Format

Send to

Choose Destination

See 1 citation found using an alternative search:

Biochem J. 2014 Mar 1;458(2):203-11. doi: 10.1042/BJ20131350.

Hypoxia-inducible factors regulate human and rat cystathionine β-synthase gene expression.

Author information

1
§Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, Chicago, IL 60637, U.S.A.
2
‡Department of Biochemistry, School of Medicine, Keio University, Tokyo 160-8582, Japan.

Abstract

Increased catalytic activity of CBS (cystathionine β-synthase) was recently shown to mediate vasodilation of the cerebral microcirculation, which is initiated within minutes of the onset of acute hypoxia. To test whether chronic hypoxia was a stimulus for increased CBS expression, U87-MG human glioblastoma and PC12 rat phaeochromocytoma cells were exposed to 1% or 20% O2 for 24-72 h. CBS mRNA and protein expression were increased in hypoxic cells. Hypoxic induction of CBS expression was abrogated in cells transfected with vector encoding shRNA targeting HIF (hypoxia-inducible factor) 1α or 2α. Exposure of rats to hypobaric hypoxia (0.35 atm; 1 atm=101.325 kPa) for 3 days induced increased CBS mRNA, protein and catalytic activity in the cerebral cortex and cerebellum, which was blocked by administration of the HIF inhibitor digoxin. HIF-binding sites, located 0.8 and 1.2 kb 5' to the transcription start site of the human CBS and rat Cbs genes respectively, were identified by ChIP assays. A 49-bp human sequence, which encompassed an inverted repeat of the core HIF-binding site, functioned as a hypoxia-response element in luciferase reporter transcription assays. Thus HIFs mediate tissue-specific CBS expression, which may augment cerebral vasodilation as an adaptive response to chronic hypoxia.

PMID:
24328859
PMCID:
PMC4374488
DOI:
10.1042/BJ20131350
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center