Ändra sökning
Avgränsa sökresultatet
1 - 30 av 30
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Dånmark, Staffan
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Gladnikoff, Micha
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Frisk, Thomas
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Mustafa, Kamal
    Russom, Aman
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik.
    Finne-Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Development of a novel microfluidic device for long-term in situ monitoring of live cells in 3-dimensional matrices2012Ingår i: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 14, nr 5, s. 885-893Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Using the latest innovations in microfabrication technology, 3-dimensional microfluidic cell culture systems have been developed as an attractive alternative to traditional 2-dimensional culturing systems as a model for long-term microscale cell-based research. Most microfluidic systems are based on the embedding of cells in hydrogels. However, physiologically realistic conditions based on hydrogels are difficult to obtain and the systems are often too complicated. We have developed a microfluidic cell culture device that incorporates a biodegradable rigid 3D polymer scaffold using standard soft lithography methods. The device permits repeated high-resolution fluorescent imaging of live cell populations within the matrix over a 4 week period. It was also possible to track cell development at the same spatial location throughout this time. In addition, human primary periodontal ligament cells were induced to produce quantifiable calcium deposits within the system. This simple and versatile device should be readily applicable for cell-based studies that require long-term culture and high-resolution bioimaging.

  • 2.
    Dånmark, Staffan
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Polymerteknologi.
    Gladnikoff, Micha
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Polymerteknologi.
    Frisk, Thomas
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Mustafa, Kamal
    Insititutt for klinisk Odontologi, Medicinska och Odontologiska Fakulteten, Universitetet i Bergen, Norge.
    Russom, Aman
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Finne-Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Polymerteknologi.
    Development of Novel Microfluidic Device for Long-Term in situ Monitoring of Live Cells in 3-dimensional MatricesManuskript (preprint) (Övrigt vetenskapligt)
  • 3.
    Errando-Herranz, Carlos
    et al.
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Vastesson, Alexander
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Pardon, Gaspard
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Bergström, Gunnar
    Wijngaart, Wouter van der
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Haraldsson, Tommy
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Brismar, Hjalmar
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Gylfason, Kristinn B.
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Biocompatibility of OSTE polymers studied by cell growth experiments2013Ingår i: Proceedings of the 17th Int. Conf. on Miniaturized Systems for Chemistry  and Life Sciences (microTAS), Freiburg, Germany, 2013Konferensbidrag (Refereegranskat)
    Abstract [en]

    The recently introduced OSTE polymer technology has shown very useful features for microfluidics for lab-on-a-chip applications. However, no data has yet been published on cell viability on OSTE. In this work, we study the biocompatibility of three OSTE formulations by cell growth experiments. Moreover, we investigate the effect of varying thiol excess on cell viability on OSTE surfaces. The results show poor cell viability on one OSTE formulation, and viability comparable with polystyrene on a second formulation with thiol excess below 60%. In the third formulation, we observe cell proliferation. These results are promising for cell-based assays in OSTE microfluidic devices.

    Ladda ner fulltext (pdf)
    fulltext
  • 4. Fenton, Robert A.
    et al.
    Moeller, Hanne B.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Snaebjornsson, Marteinn T.
    Holen, Torgeir
    MacAulay, Nanna
    Differential water permeability and regulation of three aquaporin 4 isoforms2010Ingår i: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 67, nr 5, s. 829-840Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aquaporin 4 (AQP4) is expressed in the perivascular glial endfeet and is an important pathway for water during formation and resolution of brain edema. In this study, we examined the functional properties and relative unit water permeability of three functional isoforms of AQP4 expressed in the brain (M1, M23, Mz). The M23 isoform gave rise to square arrays when expressed in Xenopus laevis oocytes. The relative unit water permeability differed significantly between the isoforms in the order of M1 > Mz > M23. None of the three isoforms were permeable to small osmolytes nor were they affected by changes in external K+ concentration. Upon protein kinase C (PKC) activation, oocytes expressing the three isoforms demonstrated rapid reduction of water permeability, which correlated with AQP4 internalization. The M23 isoform was more sensitive to PKC regulation than the longer isoforms and was internalized significantly faster. Our results suggest a specific role for square array formation.

  • 5. Gunnarson, E.
    et al.
    Axehult, G.
    Baturina, G.
    Zelenin, S.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Aperia, A.
    Lead induces increased water permeability in astrocytes expressing aquaporin 42005Ingår i: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 136, nr 1, s. 105-114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The water channel aquaporin 4 (AQP4) is abundantly expressed in astrocytes. There is now compelling evidence that AQP4 may contribute to an unfavorable course in brain edema. Acute lead intoxication is a condition that causes brain damage preceded by brain edema. Here we report that lead increases AQP4 water permeability (P-f) in astrocytes. A rat astrocyte cell line that does not express aquaporin 4 was transiently transfected with aquaporin 4 tagged with green fluorescent protein (GFP). Using confocal laser scanning microscopy we measured water permeability in these cells and in AQP4-negative cells located on the same plate. AQP4-expressing astrocytes had a three-fold higher water permeability than astrocytes not expressing AQP4. Lead exposure induced a significant, 40%, increase in water permeability in astrocytes expressing AQP4, but had no effect on Pf in astrocytes not expressing AQP4. The increase in water permeability persisted after lead washout, while treatment with a lead chelator, meso-2,3-dimercaptosuccinic acid, abolished the lead-induced increase in Pf. The effect of lead was attenuated in the presence of a calcium (Ca2+)/ calmodulin-dependent protein kinase 11 (CaMKII) inhibitor, but not in the presence of a protein kinase C inhibitor. In cells expressing AQP4 where the consensus site for CaMKII phosphorylation was mutated, lead failed to increase water permeability. Lead exposure also increased Pf in rat astroglial cells in primary culture, which express endogenous AQP4. Lead had no effect on Pf in astrocytes transfected with aquaporin 3. In situ hybridization studies on rat brain after oral lead intake for three days showed no change in distribution of AQP4 mRNA. It is suggested that lead-triggered stimulation of water transport in AQP4-expressing astrocytes may contribute to the pathology of acute lead intoxication.

  • 6.
    Gunnarson, E
    et al.
    Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Zelenina, Marina
    Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Aperia, Anita
    Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Regulation of brain aquaporins2004Ingår i: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 129, nr 4, s. 947-955Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Emerging evidence suggests that brain aquaporins (AQP) play important roles for the dynamic regulation of brain water homeostasis and for the regulation of cerebrospinal fluid production. This review deals with the short- and long-term regulation of AQP4 and AQP9, both expressed in astrocytes, and of AQP1, expressed in the choroid plexus. AQP1 and 4 have in other cell types been shown to be regulated by phosphorylation. Phosphorylation affects the gating of AQP4 and the trafficking and insertion into membrane of AQP1. Mercury inhibits the water permeability of AQP1 and AQP9, but not AQP4. The permeability of AQP4 is increased by lead. AQP4 is also regulated by protein-protein interaction. The assembly between AQP4 and syntrophin is required for the proper localization of AQP4 in the astrocyte plasma membrane that faces capillaries. There is evidence from studies on peripheral tissues that steroid hormones regulate the expression of AQP1, AQP4 and AQP9. There is also evidence that the expression of AQP1 can be regulated by ubiquitination, and that osmolality can regulate the expression of AQP1, AQP4 and AQP9. Further insight into the mechanisms by which brain AQPs are regulated will be of utmost clinical importance, since perturbed water flow via brain AQPs has been implicated in many neurological diseases and since, in brain edema, water flow via AQP4 may have a harmful effect.

  • 7. Gunnarson, E.
    et al.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Song, Yutong
    Illarionova, N.
    Brismar, Hjalmar
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Andersson, Ulf
    Zelenin, S.
    Aperia, Anita
    Effect of the brain protecting agent erythropoietin on astrocyte function2009Konferensbidrag (Refereegranskat)
  • 8. Gunnarson, Eli
    et al.
    Song, Yutong
    Kowalewski, Jacob M
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Brismar, Hjalmar
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Brines, Michael
    Cerami, Anthony
    Andersson, Ulf
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Aperia, Anita
    Erythropoietin modulation of astrocyte water permeability as a component of neuroprotection.2009Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 1091-6490, Vol. 106, nr 5, s. 1602-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Disturbed brain water homeostasis with swelling of astroglial cells is a common complication in stroke, trauma, and meningitis and is considered to be a major cause of permanent brain damage. Astroglial cells possess the water channel aquaporin 4 (AQP4). Recent studies from our laboratory have shown that glutamate, acting on group I metabotropic glutamate receptors (mGluRs), increases the permeability of astrocyte AQP4, which, in situations of hypoxia-ischemia, will increase astrocyte water uptake. Here we report that erythropoietin (EPO), which in recent years has emerged as a potent neuro-protective agent, antagonizes the effect of a group I mGluR agonist on astrocyte water permeability. Activation of group I mGluRs triggers fast and highly regular intracellular calcium oscillations and we show that EPO interferes with this signaling event by altering the frequency of the oscillations. These effects of EPO are immediate, in contrast to the neuroprotective effects of EPO that are known to depend upon gene activation. Our findings indicate that EPO may directly reduce the risk of astrocyte swelling in stroke and other brain insults. In support of this conclusion we found that EPO reduced the neurological symptoms in a mouse model of primary brain edema known to depend upon AQP4 water transport.

  • 9. Gunnarson, Eli
    et al.
    Zelenina, Marina
    Axehult, Gustav
    Song, Yutong
    Bondar, Alexander
    Krieger, Patrik
    Brismar, Hjalmar
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Zelenin, Sergey
    Aperia, Anita
    Identification of a molecular target for glutamate regulation of astrocyte water permeability2008Ingår i: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 56, nr 6, s. 587-596Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Astrocytes play a key role for maintenance of brain water homeostasis, but little is known about mechanisms of short-term regulation of astrocyte water permeability. Here, we report that glutamate increases astrocyte water permeability and that the molecular target for this effect is the aquaporin-4 (AQP4) serine 111 residue, which is in a strategic position for control of the water channel gating. The glutamate effect involves activation of group I metabotropic glutamate receptors (mGluR), intracellular calcium release, and activation of calcium/calmodulin-dependent protein kinase II (CaMKII) and nitric oxide synthase (NOS). The physiological impact of our results is underlined by the finding that mGluR activation increases the rate of hypoosmotic tissue swelling in acute rat hippocampal slices. Cerebral ischemia is associated with an excessive release of glutamate, and in postischemic cerebral edema ablation of AQP4 attenuates the degree of damage. Thus, we have identified AQP4 as the molecular target for drugs that may attenuate the development of brain edema.

  • 10. Gunnarson, Eli
    et al.
    Zelenina, Marina
    Karolinska Institutet.
    Song, Yutong
    Kowalewski, Jacob M.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Brismar, Hjalmar
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Brines, Michael
    Cerami, Antony
    Andersson, Ulf
    Aperia, Anita
    Kvinnor och barns hälsa, Karolinska Institutet.
    Erythropoietin modulation of astrocyte water permeability: a potential component of neuroprotection2008Ingår i: Neuroscience 2008, 2008Konferensbidrag (Refereegranskat)
  • 11.
    Kamali-Zare, Padideh
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Kowalewski, Jacob M
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Aperia, Anita
    Önfelt, Björn
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Brismar, Hjalmar
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Role of diffusion limited space on water and salt homeostasisManuskript (preprint) (Övrigt vetenskapligt)
  • 12. Li, Yanhong
    et al.
    Marcoux, Marie-Odile
    Gineste, Martine
    Vanpee, Mireille
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Casper, Charlotte
    Expression of water and ion transporters in tracheal aspirates from neonates with respiratory distress2009Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 98, nr 11, s. 1729-1737Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: The aim of the study was to determine whether neonatal respiratory distress is related to changes in water and ion transporter expression in lung epithelium. Methods: The study included 32 neonates on mechanical ventilation: 6 patients with normal lung X-rays (control group), eight with respiratory distress syndrome (RDS), eight with transient tachypnea of the newborn (TTN), 10 with abnormal lung X-rays (mixed group). The protein abundance of water channel AQP5, epithelial sodium channel (ENaC; alpha-, beta- and gamma-ENaC) and Na+, K+-ATPase alpha 1 were examined in tracheal aspirates using semiquantitative immunoblotting. Results: beta-ENaC level was significantly lower in RDS group compared with infants with TTN and infants in the control group. AQP5 expression was significantly higher in TTN compared with the infants with RDS and all other infants with abnormal lung X-rays. Conclusion: Neonatal respiratory distress is associated with changes in beta-ENaC and AQP5 expression. The lower beta-ENaC expression may be one of the factors that predispose to the development of RDS. The higher AQP5 expression may provide the possibility for reabsorption of postnatal lung liquid, which contributes to quick recovery of infants with TTN.

  • 13. Li, Yanhong
    et al.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik. Karolinska Institutet, Sweden.
    Plat-Willson, Genevieve
    Marcoux, Marie-Odile
    Aperia, Anita
    Casper, Charlotte
    Urinary aquaporin-2 excretion during ibuprofen or indomethacin treatment in preterm infants with patent ductus arteriosus2011Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 100, nr 1, s. 59-66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: Water channel AQP2 is the target for vasopressin (AVP) and a major determinant of urinary concentrating capacity. In mature kidneys, prostaglandins counteract the effect of AVP on AQP2 expression at functional sites. We investigated whether disturbances in water homeostasis in infants with patent ductus arteriosus (PDA) treated with prostaglandin inhibitors can be attributed to activation of AQP2. Methods: In 53 infants with symptomatic PDA (gestational age 24-33 weeks), 30 receiving ibuprofen and 23 indomethacin starting at 2-15 days of life, clinical and biochemical data were collected before treatment and after each dose of the drugs. Urinary AQP2 was determined by dot immunoblotting. Results: Urinary AQP2 level and osmolality were decreased in both groups. Urinary osmolality was overall low and correlated inversely with fluid uptake. In ibuprofen group, there was no correlation of AQP2 level with urinary osmolality. Conclusion: There was no AQP2 upregulation in the infants. The low urinary osmolality and dissociation between urinary osmolality and urinary AQP2 level indicate that the fluid retention sometimes observed in PDA infants treated with prostaglandin inhibitors is not caused by increased levels of functional AQP2. Thus, knowledge about the renal physiology of the adult cannot always be transferred to the infant kidney.

  • 14. Nejsum, Lene N.
    et al.
    Zelenina, Marina
    Karolinska Institutet.
    Aperia, Anita
    Frøkiaer, Jørgen
    Nielsen, Søren
    Bidirectional regulation of AQP2 trafficking and recycling: involvement of AQP2-S256 phosphorylation2005Ingår i: American Journal of Physiology: Renal Physiology, ISSN 1931-857X, Vol. 288, nr 5, s. F930-F938Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The present study examined the role of PKA and serine256 (S256) phosphorylation for AQP2 trafficking and recycling using cells transfected with wild-type AQP2 (AQP2-WT) or mutant AQP2 and high-resolution confocal microscopic techniques. In transiently transfected MDCK-C7 cells, stimulation with forskolin induced translocation of AQP2-WT to the plasma membrane. Treatment of AQP2-WT cells with the PKA inhibitor H-89 following forskolin stimulation resulted in internalization of AQP2-WT. Moreover, H-89 treatment of AQP2-S256D (mimicking constitutively phosphorylated AQP2 and hence localized to the plasma membrane) resulted in redistribution of AQP2-S256D to intracellular vesicles, even in the presence of forskolin. Both PGE2 and dopamine stimulation induced endocytosis of AQP2-WT and AQP2-S256D, respectively, in forskolin-stimulated cells. Consistent with this, dopamine in the presence of vasopressin stimulated endocytosis of AQP2 in slices of rat kidney inner medulla without substantial dephosphorylation. In conclusion, these results strongly suggest that 1) S256 phosphorylation is necessary but not sufficient for AQP2 plasma membrane expression, 2) active PKA is required for AQP2 plasma membrane expression, 3) PGE2 and dopamine induce internalization of AQP2 independently of AQP2 dephosphorylation, and 4) preceding activation of cAMP production is necessary for PGE2 and dopamine to cause AQP2 internalization.

  • 15. Ringman, Andreas
    et al.
    Zelenina, Marina
    Department of Woman and Child Health, Astrid Lindgren Children's Hospital Research Laboratory Q2:09, Karolinska Institutet.
    Eklöf, Ann-Christine
    Aperia, Anita
    Department of Woman and Child Health, Astrid Lindgren Children's Hospital Research Laboratory Q2:09, Karolinska Institutet.
    Frenckner, Björn
    NKCC-1 and ENaC are down-regulated in nitrofen-induced hypoplastic lungs with congenital diaphragmatic hernia2008Ingår i: Pediatric surgery international (Print), ISSN 0179-0358, E-ISSN 1437-9813, Vol. 24, nr 9, s. 993-1000Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Congenital diaphragmatic hernia (CDH) is accompanied by pulmonary hypoplasia and pulmonary hypertension. Fetal lung growth is dependent on the secretion of lung liquid, which normally is absorbed at partus. The ion channel NKCC-1 is involved in this secretory process, but has recently also been reported to be implicated in absorption. CDH patients show a disturbed transition from secretion to absorption. alpha- and beta-ENaC are essential for lung liquid absorption. Common for all transcellular ion transport is the need for Na/K-ATPase as a primary driving force. The aim of the study was first to map the normal pulmonary expression of the above proteins during late gestation and secondly to see if the expression was affected in a CDH rat model. Pregnant Sprague-Dawley rat dams were given nitrofen on gestational day 9.5 to induce CDH. The fetuses were removed on gestational days E18 and E21. In addition, newborn rats were harvested postpartum on day P2. The fetuses were put into one of two groups: hypoplastic lungs without CDH (N-CDH) and hypoplastic lungs with CDH (N+CDH). The pulmonary expression of NKCC-1, alpha-/beta-ENaC and Na/K-ATPase was then analyzed using Western blot. We found that the protein levels of NKCC-1 on gestational days E18 and E21 were significantly lower among fetuses with N+CDH as well as N-CDH compared to controls. The expression of beta-ENaC was also significantly down-regulated in both the groups on E18 and E21. The protein levels of alpha-ENaC and Na/K-ATPase were not found to be significantly decreased, but both showed a tendency towards down-regulation. The marked down-regulation of NKCC-1 in fetal hypoplastic lungs with CDH indicates a possibly decreased lung liquid production. This may be one of the mechanisms behind the disturbed pulmonary development in CDH. We also show that beta-ENaC is down-regulated. Down-regulation of beta-ENaC may result in abnormal lung liquid absorption, which could be one of the mechanisms behind the respiratory distress seen in CDH patients postpartum.

  • 16. Ringman Uggla, Andreas
    et al.
    von Schewelov, Katarina
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Aperia, Anita
    Nordic Centre of Excellence for Research in Water Imbalance Related Disorders (WIRED), Stockholm, Sweden.
    Frenckner, Björn
    Low pulmonary expression of epithelial Na(+) channel and Na(+), K(+)-ATPase in newborn infants with congenital diaphragmatic hernia2011Ingår i: Neonatology, ISSN 1661-7800, E-ISSN 1661-7819, Vol. 99, nr 1, s. 14-22Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: It has been suggested from several animal studies and clinical observations that congenital diaphragmatic hernia (CDH) with pulmonary hypoplasia is accompanied by a disturbed perinatal ion transport. This could lead to respiratory distress due to slower clearance of fetal lung fluid at birth.

    OBJECTIVES: The purpose of this study was to determine whether CDH is related to changes in the expression of three rate-limiting transporter proteins in lung epithelium at birth.

    METHODS: Tracheal aspirate was collected from 12 newborn infants with CDH and from 8 newborn control patients. Sampling was performed at postnatal age 18 and at 43 h in the CDH group and at 18 h in the control group. The protein abundance of α-, β- and γ-epithelial Na(+) channel (ENaC), aquaporin 5 and Na(+), K(+)-ATPase α(1) was analyzed using semiquantitative immunoblotting.

    RESULTS: The levels of β-ENaC, γ-ENaC and Na(+), K(+)-ATPase α(1) collected at 18 h postnatally were significantly lower in CDH infants compared to control infants. In the CDH group, no significant difference in the expression of the ENaC subunits, Na(+), K(+)-ATPase α(1) or aquaporin 5 could be detected between the two sampling time points.

    CONCLUSIONS: This downregulation may result in an abnormal lung fluid absorption which could be an important mechanism behind the respiratory distress seen in newborn CDH patients.

  • 17. Rodionova, Elena A.
    et al.
    Kuznetsova, Alla A.
    Shakhmatova, Elena I.
    Prutskova, Natalia
    Nielsen, Søren
    Holtbäck, Ulla
    Natochin, Yuri
    Zelenina, Marina
    Nordic Center of Excellence for Research in Water Imbalance Related Disorders (WIRED), Department of Woman and Child Health, Karolinska Institutet.
    Urinary aquaporin-2 in children with acute pyelonephritis2006Ingår i: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 21, nr 3, s. 361-367Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Children with acute pyelonephritis develop polyuria and have reduced maximum urinary concentration capacity. We studied whether these abnormalities are associated with altered urinary excretion of the water channel aquaporin-2 (AQP2) in the renal collecting duct. AQP2 is the main target for antidiuretic action of arginine vasopressin (AVP), and the urinary excretion of this protein is believed to be an index of AVP signaling activity in the kidney. Children with acute pyelonephritis, aged 5-14 years, were examined for urinary flow rate, creatinine clearance, unchallenged urine osmolality, and urinary ion excretion. Urinary excretion of AQP2 was measured by dot immunoblotting technique. Studies were performed in the acute phase of pyelonephritis, in the same children after treatment, and in control patients. At the onset of pyelonephritis, urinary flow rate and solute excretion were increased, but the urinary osmolality was unchanged. The urinary level and urinary excretion of AQP2 was increased in acute pyelonephritis and decreased after treatment. Excretion of aquaporin-3 was unchanged, suggesting that the increase in AQP2 urinary excretion was not due to a shedding of collecting duct cells. The results suggest that a mechanism proximal to the collecting duct may be responsible for the polyuria observed in children with acute pyelonephritis. Increased urinary AQP2 levels suggest that a compensatory activation of apical plasma membrane targeting of AQP2 may occur in pyelonephritis.

  • 18. Takenaga, Keizo
    et al.
    Nygren, Jim
    Zelenina, Marina
    Department of Woman and Child Health, Karolinska Institutet.
    Ohira, Miki
    Iuchi, Toshihiko
    Lukanidin, Eugen
    Sjöquist, Mats
    Kozlova, Elena N.
    Modified expression of Mts1/S100A4 protein in C6 glioma cells or surrounding astrocytes affects migration of tumor cells in vitro and in vivo2007Ingår i: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 25, nr 3, s. 455-563Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The calcium-binding Mts1/S100A4 protein plays an important role in motility and metastatic activity of tumor cells. Recently we showed that Mts1/S100A4 is expressed in white matter astrocytes and influences their migration in vitro and in vivo. Here, we have investigated the role of Mts1/S100A4 expression in C6 glioma cells or surrounding astrocytes for migration of C6 cells on astrocytes, using short interference (si) RNA to silence Mts1/S100A4 expression. We find that in vitro, the migration of Mts1/S100A4 expressing and silenced C6 cells on astrocytes is predominantly dependent on the expression of Mts1/S100A4 in astrocytes, i.e. C6 cells preferably migrate on Mts1/S100A4-silenced astrocytes. In vivo, Mts1/S100A4-positive C6 cells preferably migrate in white matter. In contrast Mts1/S100A4-silenced C6 cells avoid white matter and migrate in gray matter and meninges. Thus, the migration pattern of C6 cells is affected by their intrinsic Mts1/S100A4 expression as well as Mts1/S100A4 expression in astrocytes. To investigate if Mts1/S100A4 has a significant role on brain tumor progression, we made quantitative RT-PCR analysis for the expression of S100A4/Mts1 in various grades of astrocytic tumors. Our data showed that high-grade glioblastomas express higher amount of S100A4/Mts1 than low-grade astrocytic tumors.

  • 19. Tritto, Simona
    et al.
    Gastaldi, Giulia
    Zelenin, Sergey
    Grazioli, Monica
    Orsenigo, Maria Novella
    Ventura, Ulderico
    Laforenza, Umberto
    Zelenina, Marina
    Nordic Centre of Excellence for Research in Water Imbalance Related Disorders, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Osmotic water permeability of rat intestinal brush border membrane vesicles: involvement of aquaporin-7 and aquaporin-8 and effect of metal ions2007Ingår i: Biochemistry and Cell Biology, ISSN 0829-8211, E-ISSN 1208-6002, Vol. 85, nr 6, s. 675-684Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Water channels AQP7 and AQP8 may be involved in transcellular water movement in the small intestine. We show that both AQP7 and AQP8 mRNA are expressed in rat small intestine. Immunoblot and immunohistochemistry experiments demonstrate that AQP7 and AQP8 proteins are present in the apical brush border membrane of intestinal epithelial cells. We investigated the effect of several metals and pH on the osmotic water permeability (Pf) of brush border membrane vesicles (BBMVs) and of AQP7 and AQP8 expressed in a cell line. Hg2+, Cu2+, and Zn2+ caused a significant decrease in the BBMV Pf, whereas Ni2+ and Li+ had no effect. AQP8-transfected cells showed a reduction in Pf in the presence of Hg2+ and Cu2+, whereas AQP7-transfected cells were insensitive to all tested metals. The Pf of both BBMVs and cells transfected with AQP7 and AQP8 was not affected by pH changes within the physiological range, and the Pf of BBMVs alone was not affected by phlorizin or amiloride. Our results indicate that AQP7 and AQP8 may play a role in water movement via the apical domain of small intestine epithelial cells. AQP8 may contribute to the water-imbalance-related clinical symptoms apparent after ingestion of high doses of Hg2+ and Cu2+.

  • 20.
    Turdalieva, Aizat
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Solandt, Johan
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab. AstraZeneca, Sweden.
    Xu, Hao
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Shambetova, Nestan
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Blom, Hans
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Fu, Ying
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Defence of liquid-covered Calu-3 epithelial cell monolayer against multiple depositions of 3-mercaptopropionic-acid coated CdSe-CdS/ZnS quantum dotsManuskript (preprint) (Övrigt vetenskapligt)
  • 21. Uematsu, Ken
    et al.
    Heiman, Myriam
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Padovan, Julio
    Chait, Brian T.
    Aperia, Anita
    Nishi, Akinori
    Greengard, Paul
    Protein kinase A directly phosphorylates metabotropic glutamate receptor 5 to modulate its function2015Ingår i: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 132, nr 6, s. 677-686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Metabotropic glutamate receptor 5 (mGluR5) regulates excitatory post-synaptic signaling in the central nervous system (CNS) and is implicated in various CNS disorders. Protein kinase A (PKA) signaling is known to play a critical role in neuropsychiatric disorders such as Parkinson's disease, schizophrenia, and addiction. Dopamine signaling is known to modulate the properties of mGluR5 in a cAMP-and PKA-dependent manner, suggesting that mGluR5 may be a direct target for PKA. Our study identifies mGluR5 at Ser870 as a direct substrate for PKA phosphorylation and demonstrates that this phosphorylation plays a critical role in the PKA-mediated modulation of mGluR5 functions such as extracellular signal-regulated kinase phosphorylation and intracellular Ca2+ oscillations. The identification of the molecular mechanism by which PKA signaling modulates mGluR5-mediated cellular responses contributes to the understanding of the interaction between dopaminergic and glutamatergic neuronal signaling.

  • 22. Uggla, Andreas Ringman
    et al.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Eklöf, Ann-Christine
    Aperia, Anita
    Frenckner, Björn
    Expression of chloride channels in trachea-occluded hyperplastic lungs and nitrofen-induced hypoplastic lungs in rats2009Ingår i: Pediatric surgery international (Print), ISSN 0179-0358, E-ISSN 1437-9813, Vol. 25, nr 9, s. 799-806Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Congenital diaphragmatic hernia is accompanied by pulmonary hypoplasia. Fetal lung growth is dependent on the secretion of lung liquid, in which Cl- secretion by the pulmonary epithelium plays a crucial role. A decrease of lung liquid production during fetal development renders marked pulmonary hypoplasia, while accelerated fetal lung growth in the form of pulmonary hyperplasia can be achieved by in utero tracheal occlusion (TO). Cl- secretion presumably involves NKCC-1, the primary basolateral Cl- entry pathway in airway epithelia, coupled to an apical Cl- exit pathway. The chloride channels ClC-2, -3 and -5, members of the CLC gene family, are all localized to the apical membrane of fetal respiratory epithelia, which makes them possible candidates for being mediators of fetal apical Cl- secretion. The aim of the study was to examine the potential of ClC-2, -3 and -5 as alternative apical airway epithelial Cl- channels in normal lung development and their possible role in the development of hypoplastic lungs in CDH. We also wanted to examine ClC-2, -3 and -5 together with the NKCC-1 in hyperplastic lungs created by TO. Pregnant Sprague-Dawley rat dams were given nitrofen on gestational day 9.5 to induce pulmonary hypoplasia. Controls were given only olive oil. The rat fetuses were removed on days 17, 19 and 21. Hyperplastic lungs were created by intrauterine TO of rat fetuses on day 19 and the lungs were harvested on day 21. The pulmonary expression of ClC-2, -3, -5 and NKCC-1 was then analyzed using Western blot. We found that the temporal expression of ClC-2 and -3 in normal fetal lungs points toward a developmental regulation. ClC-2 and -3 were also both down-regulated on day 21 in hypoplastic CDH lungs. In TO induced hyperplastic lungs, the levels of ClC-2 were found to be significantly up-regulated. NKCC-1 showed a tendency toward up-regulation in hyperplastic lungs, while ClC-3 showed a tendency to be down-regulated, but no statistically significant changes could be seen. There was no difference between controls and any of the groups for the expression of ClC-5. We show that the developmental changes in ClC-2 and ClC-3 protein expression are negatively affected in hypoplastic CDH lungs. Lung hyperplasia created by TO up-regulates the expression of ClC-2. ClC-2 is therefore an interesting potential target in the development of novel, non-invasive, therapies for CDH treatment.

  • 23. Vieux, Rachel
    et al.
    Zelenina, Marina
    Nordic Center of Excellence for Research in Water Imbalance Related Disorders (WIRED), Karolinska Institutet, Stockholm, Sweden. Department of Women's and Children's Health, Karolinska Institutet.
    Aperia, Anita
    Nordic Center of Excellence for Research in Water Imbalance Related Disorders (WIRED), Karolinska Institutet, Stockholm, Sweden. Department of Women's and Children's Health, Karolinska Institutet.
    Hascoët, Jean-Michel
    The renal adverse effects of ibuprofen are not mediated by AQP2 water channels2010Ingår i: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 25, nr 7, s. 1277-1284Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to determine (1) whether ibuprofen treatment in very preterm infants causes an increase in the renal water channel aquaporin-2 (AQP2) activity in the collecting duct via prostaglandin synthesis inhibition and (2) whether AQP2 activity remains disturbed long after ibuprofen treatment has ended. This was a prospective study involving premature infants with a gestation age of 27-31 weeks who received treatment between December 2005 and August 2006 in a tertiary Neonatal Intensive Care Unit. Each ibuprofen-treated infant was matched to two controls. Renal glomerular and tubular function were evaluated weekly for 1 month, and urinary AQP2 was measured by immuno-dotting. In total, 166 longitudinal samples were analyzed in 36 infants. Median [interquartile range] gestational age and birthweight were 28 [27.0-29.5] weeks and 1160 [1041-1242] g, respectively. Perinatal factors were similar in both groups. Urine output was significantly decreased in the ibuprofen-treated infants during the treatment. The urinary AQP2 level decreased significantly from day 2 to day 7 in both groups and was similar thereafter for the first month of life in ibuprofen-treated and control groups. Based on our results, we conclude that ibuprofen-induced oligo-anuria is not associated with a change in AQP2 activity and that ibuprofen does not affect AQP2 activity during the first month of life in very preterm neonates.

  • 24. Zelenin, Sergey
    et al.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik. Karolinska Inst, Stockholm, Sweden.
    Li, Yanhong
    Kamali-Zare, Padideh
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik. Karolinska Inst, Stockholm, Sweden.
    Bondar, Alexander
    Brismar, Hjalmar
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik. Karolinska Inst, Stockholm, Sweden.
    Aperia, Anita
    AQP4 role in renal K+ transport2009Ingår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 23, s. 867.2-Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    The collecting duct principle cells (PC) play a major role for concentration of urine and regulation of K+ homeostasis. Two water channels, AQP3 and AQP4, are expressed in the PC basolateral membrane (BLM). Here we present evidence that AQP4 participates in regulation of renal K+ transport. K+ enters the cell via Na+,K+-ATPase mediated transport in BLM. The presence of K+ channels in BLM, which is deeply infolded, thus providing a diffusion limited space, permits K+ recirculation, considered important for maintenance of membrane potential. Here we show with co-immunoprecipitation and GST pulldown assays, that in rat renal papilla, AQP4, but not AQP3, assembles with Na+,K+-ATPase and the K+ channel Kir7.1. This led us to hypothesize that AQP4, Na+,K+-ATPase and Kir7.1 form a K+ transporting microdomain, where AQP4 water transport maintains a favorable gradient for K+ efflux and stabilizes membrane potential. A mathematical model of K+ transport across an epithelial cells with a deeply infolded BLM supported the hypothesis and predicted an even higher impact of AQP water transport on K+ transport if AQP water permeability is sensitive to fluctuations in extracellular K+ concentration ([K+]o). To test this, AQP3 and AQP4 were expressed in MDCK cells, a cell line with much in common with PC. Water permeability was increased when [K+]o was 12mM in cells expressing AQP4 but not in cells expressing AQP3.

  • 25. Zelenina, M.
    et al.
    Brismar, Hjalmar
    Osmotic water permeability measurements using confocal laser scanning microscopy2000Ingår i: European Biophysics Journal, ISSN 0175-7571, E-ISSN 1432-1017, Vol. 29, nr 3, s. 165-171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have developed a method for measurement of plasma membrane water permeability (P-f) in intact cells using laser scanning confocal microscopy. The method is based on confocal recording of the fluorescence intensity emitted by calcein-loaded adherent cells during osmotic shock. P-f is calculated as a function of the time constant in the fluorescence intensity change, the cell surface-to-volume ratio and the fractional content of the osmotically active cell volume. The method has been applied to the measurement of water permeability in MDCK cells. The cells behaved as linear osmometers in the interval from 100 to 350 mosM. About 57% of the total cell volume was found to be osmotically inactive. Water movement across the plasma membrane in intact MDCK cells was highly temperature dependent. HgCl2 had no effect on water permeability, while amphotericin B and DMSO significantly increased P-f values. The water permeability in MDCK cells transfected with aquaporin 2 was an order of magnitude higher than in the intact MDCK cell line. The water permeability of the nuclear membrane in both cell lines was found to be unlimited. Thus the intranuclear fluid belongs to the osmotically active portion of the cell. We conclude that the use of confocal microscopy provides a sensitive and reproducible method for measurement of water permeability in different types of adherent cells and potentially for coverslip-attached tissue preparations.

  • 26.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Regulation of brain aquaporins2010Ingår i: Neurochemistry International, ISSN 0197-0186, E-ISSN 1872-9754, Vol. 57, nr 4, s. 468-488Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Three aquaporins are expressed in the brain. AQP4, the predominant brain water channel, is expressed in astrocyte endfeet facing brain capillaries, perisynaptic spaces, and nodes of Ranvier. It is implicated in brain edema formation and resolution. It is also believed to assist clearance of K+. released during neuronal activity. AQP1 is expressed in epithelial cells of choroid plexus and is implicated in cerebrospinal fluid formation. AQP9, which has been reported to be present in astrocytes and in subpopulations of neurons, is implicated in the brain energy metabolism. All three brain AQPs are strongly upregulated in brain tumors and in injured brain tissue. Water and solute transport via AQPs depends on concentration gradients across the membrane, but the magnitude of the transport is to a large extent determined by the single channel permeability of AQPs and by their abundance in the cell membrane. The future therapies will have to address not only the forces driving the water and solute transport (e.g. as mannitol infusion does in the treatment of brain edema), but also the regulation of AQPs, which provide the means for water entry to the brain, for water exit from the brain, and for redistribution of water and solutes within the brain compartments. This review summarizes the data concerning structure, permeability, role in the brain, short-term and long-term regulation of the three AQPs.

  • 27.
    Zelenina, Marina
    et al.
    Nordic Centre of Excellence for Research in Water Imbalance Related Disorders (WIRED), Department of Woman and Child Health, Karolinska Institute.
    Li, Yanhong
    Glorieux, Isabelle
    Arnaud, Catherine
    Cristini, Christelle
    Decramer, Stéphane
    Aperia, Anita
    Casper, Charlotte
    Urinary aquaporin-2 excretion during early human development2006Ingår i: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 21, nr 7, s. 947-952Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study was undertaken to assess one of the determinants of kidney concentrating capacity, aquaporin-2 (AQP2), in order to understand the physiopathology of water balance in newborn babies. Urinary AQP2 excretion has been shown to be proportional to AQP2 level in the apical plasma membrane of the kidney collecting ducts and has been suggested as a marker of vasopressin (AVP) action. Urinary AQP2 excretion in the early postnatal period and at 3 weeks of age was measured in 123 neonates admitted during a 6-month period to the neonatal intensive care unit of the Children's Hospital of Toulouse, France. Clinical and biochemical data were collected for each child. During the first days after birth, higher urinary AQP2 was observed in boys than in girls (P=0.01) and positively correlated with urinary sodium/potassium (Na/K) ratio (r=0.33, P=0.01). When the babies had reached 3 weeks of age, urinary AQP2 was proportional to the gestational age at birth (r=0.33, P=0.0068) and daily weight gain (r=0.36, P=0.003). It did not correlate with urinary osmolality, which was overall very low in all babies. Urinary AQP2 was decreased in conditions of impaired renal function (r=-0.42, P=0.0005) and acidosis (P=0.03). Prenatal corticosteroid treatment had no significant impact on urinary AQP2 level. Our data show that urinary AQP2 correlates with the overall maturity of tubular function in human neonates. In babies at this early age, urinary AQP2 cannot serve as a direct marker of the renal action of AVP but reflects AQP2 expression level associated with different physiopathological conditions.

  • 28.
    Zelenina, Marina
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Li, Yanhong
    Kamali-Zare, Padideh
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Sakuraba, Shigeki
    MacAulay, Nanna
    Zelenin, Sergey
    Bondar, Alexander
    Brismar, Hjalmar
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Aperia, Anita
    A role for AQP4 in renal K+ transportManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    The principal cells of the collecting duct carry out two major tasks: concentration of urine and regulation of K+ homeostasis. Two water channels, AQP3 and AQP4, are expressed in the principal cell basolateral membrane. We propose that AQP4 participates in the regulation of K+ transport in the principal cells. K+ enters the cell via Na+, K+-ATPase-mediated transport in the basolateral membrane. The presence of K+ channels in this membrane permits some K+ recirculation, considered important for maintenance of membrane potential. Here we show that AQP4, but not AQP3, assembles with both Na+, K+-ATPase and an inwardly rectifying K+ channel Kir7.1. We hypothesize that AQP4, Na+, K+-ATPase and Kir7.1 form a K+-transporting microdomain and that AQP4 serves to maintain a favorable concentration gradient for K+ efflux into the diffusion-limited space within the deep infoldings in principal cell basal membrane. The hypothesis is tested in a mathematical model. The model predicts that the impact of AQP-mediated water transport on K+ transport is more significant if AQP water permeability is sensitive to fluctuations in extracellular K+ concentration ([K+]e). We measured water permeability of AQP4 expressed in a renal epithelial cell line and found that it is upregulated when [K+]e is increased to 8 mM, and downregulated when [K+]e is decreased to 1 mM. Studies in an oocyte system indicate that AQP4 does not possess a voltage or K+ sensor. Finally, we show that the expression of AQP4 in rat renal medulla is, in contrast to the expression of AQP2 and AQP3, resistant to changes in K+ intake. Our experimental data, together with the mathematical model, support the concept that AQP4 is involved in principal cell K+ transport processes.

  • 29.
    Zelenina, Marina
    et al.
    Department of Woman and Child Health, Karolinska Institutet.
    Tritto, Simona
    Bondar, Alexander A.
    Zelenin, Sergey
    Aperia, Anita
    Copper inhibits the water and glycerol permeability of aquaporin-32004Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 279, nr 50, s. 51939-51943Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aquaporin-3 (AQP3) is an aquaglyceroporin expressed in erythrocytes and several other tissues. Erythrocytes are, together with kidney and liver, the main targets for copper toxicity. Here we report that both water and glycerol permeability of human AQP3 is inhibited by copper. Inhibition is fast, dose-dependent, and reversible. If copper is dissolved in carbonic acid-bicarbonate buffer, the natural buffer system in our body, doses in the range of those observed in Wilson disease and in copper poisoning caused significant inhibition. AQP7, another aquaglyceroporin, was insensitive to copper. Three extracellular amino acid residues, Trp128, Ser152, and His241, were identified as responsible for the effect of copper on AQP3. We have previously shown that Ser152 is involved in regulation of AQP3 by pH. The fact that Ser152 mediates regulation of AQP3 by copper may explain the phenomenon of exquisite sensitivity of human erythrocytes to copper at acidic pH. When AQP3 was co-expressed with another AQP, only glycerol but not water permeability was inhibited by copper. Our results provide a better understanding of processes that occur in severe copper metabolism defects such as Wilson disease and in copper poisoning.

  • 30.
    Zelenina, Marina
    et al.
    Nordic Ctr. Excellence Res. WIRED, Department of Woman and Child Health, Karolinska Institutet.
    Zelenin, Sergey
    Aperia, Anita
    Water channels (aquaporins) and their role for postnatal adaptation.2005Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 57, nr 5 II, s. 47R-53RArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Birth is a transition from an underwater life in the uterus to a terrestrial life in a milieu where supply of water is limited. Rapid adaptation to the new environment is crucial for survival and health of infants. The discovery of a family of molecules-aquaporin (AQP) water channels-that are responsible for regulated water transport across cell membranes has made it possible to identify the molecular mechanisms behind the postnatal homeostatic adaptation and to better understand water imbalance-related disorders in infancy and childhood. Thirteen mammalian AQP isoforms have been identified, most of them having a unique tissue-specific pattern of expression. Most mammalian AQPs can be dynamically regulated, which makes them potential targets for the development of new drugs for diseases associated with disturbances in water homeostasis. This review deals with AQP in kidney, lung, and brain. Evidence is presented that AQPs are expressed in a specific age-dependent manner and that the timed expression of AQPs may have a crucial role during the early postnatal period.

1 - 30 av 30
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf