| Autor: |
Naoharu TAKANO, ing-Jie PENG, KUMAR, Ganesh K., LUO, Weibo, Hongxia HU, SHIMODA, Larissa A., SUEMATSU, Makoto, PRABHAKAR, Nanduri R., SEMENZA, Gregg L. |
| Předmět: |
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| Zdroj: |
Biochemical Journal; 3/1/2014, Vol. 458 Issue 2, p203-211, 9p |
| Abstrakt: |
Increased catalytic activity of CBS (cystathionine ß-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 hypoxiaresponse element in luciferase reporter transcription assays. Thus HIFsmediate tissue-specificCBSexpression, whichmay augment cerebral vasodilation as an adaptive response to chronic hypoxia. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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