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Developmental changes in HIF transcription factor in carotid body: Relevance for O-2 sensing by chemoreceptors
2005 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 58, no 1, 53-57 p.Article in journal (Refereed) Published
Abstract [en]

Before birth, the peripheral chemoreceptors located in the carotid bodies (CB) are adapted to the low fetal Po-2 and are relatively insensitive to hypoxia. After birth, the sensitivity of the CB to hypoxia is reset in response to the rise in Po-2. The mechanism underlying this resetting, which requires several days to complete, remains unknown. We have investigated the possibility that the hypoxia-inducible factors HIF-1 alpha and HIF-2 alpha, which are activated by oxygen deprivation, are involved in this resetting process. Accordingly, we used immunostaining and densitometry to quantitate the levels of the HIF-1 alpha and HIF-2 alpha proteins in the rat CB during early perinatal life and after exposure to in vivo hypoxia during adolescence. Tyrosine hydroxylase (TH) was used as a marker for catecholaminergic neurons and oxygen-sensitive cells in the CB. Double-immunostaining revealed constitutive expression of HIF-1 alpha in both glomus cells (TH+) and sustentacular cells (TH-) of the CB of adolescent rats. However, immunoreactivity toward HIF-2 alpha was restricted to glomus cells. After exposure to hypoxia (8% O-2, 6 h), the expression of HIF-1 alpha was selectively upregulated in glomus cells and apparent translocation of both HIF-1 alpha and HIF-2 alpha to the nucleus was observed. Both of these proteins were expressed constitutively in the CB during the perinatal transition period. During the first postnatal week, the intensity of immunostaining for HIF-1 alpha in glomus cells decreased markedly, whereas the level of HIF-2a remained constant. We suggest that this selective down-regulation of HIF-1 alpha may be involved in the postnatal maturation of CB responsiveness to hypoxia.

Place, publisher, year, edition, pages
2005. Vol. 58, no 1, 53-57 p.
Keyword [en]
hypoxia-inducible factor-1-alpha, hydroxylase gene-expression, tyrosine-hydroxylase, arterial chemoreceptors, factor 1-alpha, messenger-rna, newborn rats, hif-1-alpha, brain, epas1
Identifiers
URN: urn:nbn:se:kth:diva-14883DOI: 10.1203/01.pdr.0000163390.78239.eaISI: 000230252200010OAI: oai:DiVA.org:kth-14883DiVA: diva2:332924
Note
QC 20100525Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved

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Brismar, Hjalmar

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