kth.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
nNOS-derived NO modulates force production and iNO-derived NO the excitability in C2C12-derived 3D tissue engineering skeletal muscle via different NO signaling pathways
Heidelberg Univ Hosp, Inst Physiol & Pathophysiol, Cardioventilatory Muscle Physiol Lab, Heidelberg, Germany..
Heidelberg Univ Hosp, Inst Physiol & Pathophysiol, Cardioventilatory Muscle Physiol Lab, Heidelberg, Germany.;PromoCell GmbH, Heidelberg, Germany..
Heidelberg Univ Hosp, Inst Physiol & Pathophysiol, Cardioventilatory Muscle Physiol Lab, Heidelberg, Germany.;Heidelberg Univ, Ctr Integrat Infect Dis Res CIID, Dept Infect Dis, Heidelberg, Germany..
Heidelberg Univ Hosp, Inst Physiol & Pathophysiol, Cardioventilatory Muscle Physiol Lab, Heidelberg, Germany.;Heidelberg Univ, Ctr Integrat Infect Dis Res CIID, Dept Infect Dis, Heidelberg, Germany..
Show others and affiliations
2022 (English)In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 13, article id 946682Article in journal (Refereed) Published
Abstract [en]

Nitric oxide (NO) is a bioactive gas produced by one of the three NO synthases: neuronal NOS (nNOS), inducible (iNOS), and endothelial NOS (eNOS). NO has a relevant modulatory role in muscle contraction; this takes place through two major signaling pathways: (i) activation of soluble guanylate cyclase and, thus, protein kinase G or (ii) nitrosylation of sulfur groups of cysteine. Although it has been suggested that nNOS-derived NO is the responsible isoform in muscle contraction, the roles of eNOS and iNOS and their signaling pathways have not yet been clarified. To elucidate the action of each pathway, we optimized the generation of myooids, an engineered skeletal muscle tissue based on the C2C12 cell line. In comparison with diaphragm strips from wild-type mice, 180 myooids were analyzed, which expressed all relevant excitation-contraction coupling proteins and both nNOS and iNOS isoforms. Along with the biochemical results, myooids treated with NO donor (SNAP) and unspecific NOS blocker (L-NAME) revealed a comparable NO modulatory effect on force production as was observed in the diaphragm strips. Under the effects of pharmacological tools, we analyzed the myooids in response to electrical stimulation of two possible signaling pathways and NO sources. The nNOS-derived NO exerted its negative effect on force production via the sGG-PKG pathway, while iNOS-derived NO increased the excitability in response to sub-threshold electrical stimulation. These results strengthen the hypotheses of previous reports on the mechanism of action of NO during force production, showed a novel function of iNOS-derived NO, and establish the myooid as a novel and robust alternative model for pathophysiological skeletal muscle research.

Place, publisher, year, edition, pages
Frontiers Media SA , 2022. Vol. 13, article id 946682
Keywords [en]
tissue engineering, nitric oxide, calcium, force, myooid
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:kth:diva-317353DOI: 10.3389/fphys.2022.946682ISI: 000848364000001PubMedID: 36045747Scopus ID: 2-s2.0-85136867171OAI: oai:DiVA.org:kth-317353DiVA, id: diva2:1694567
Note

QC 20230612

Available from: 2022-09-09 Created: 2022-09-09 Last updated: 2024-01-17Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records

Ollech, Dirk

Search in DiVA

By author/editor
Ollech, Dirk
By organisation
BiophysicsScience for Life Laboratory, SciLifeLab
In the same journal
Frontiers in Physiology
Rheumatology and Autoimmunity

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 24 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf