Cyclic AMP Represses the Hypoxic Induction of Hypoxia-inducible Factors in PC12 Cells

被引：24

作者：

Torii, Satoru ^{[1
]}

Okamura, Norikazu ^{[1
]}

Suzuki, Yohei ^{[1
]}

Ishizawa, Toshiyuki ^{[1
]}

Yasumoto, Ken-ichi ^{[1
]}

Sogawa, Kazuhiro ^{[1
]}

机构：

[1] Tohoku Univ, Grad Sch Life Sci, Dept Biomol Sci, Sendai, Miyagi 980, Japan

来源：

JOURNAL OF BIOCHEMISTRY | 2009年 / 146卷 / 06期

关键词：

cyclic AMP; HIF-1 alpha stabilization; hypoxia; PC12; cells; protein kinase A; PAS DOMAIN PROTEIN; FACTOR-I HIF-1; PHOSPHORYLATION SITES; GENE-EXPRESSION; FACTOR-1-ALPHA; PHOSPHATASE-1; FIBROBLASTS; HIF-1-ALPHA; INHIBITION; RESPONSES;

D O I：

10.1093/jb/mvp129

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Hypoxia-inducible factor 1 (HIF-1) is a master regulator for hypoxic activation of genes for angiogenesis, hormone synthesis, glycolysis and cell survival. In addition to hypoxic stimulus, various effectors and reagents were reported to affect HIF-1 activity. Here, we show that cyclic AMP (cAMP) down-regulates the HIF-1 activity in pheochromocytoma PC12 cells but not in Hep3B and HeLa cells. Hypoxia response element-dependent reporter activity was decreased by the addition of dibutyryl cAMP. Expression of protein kinase A (PKA) catalytic alpha-subunits repressed the HIF-1 activity. HIF-1 alpha and HLF (HIF-2 alpha or EPAS1) protein levels were decreased by the treatment with dibutyryl cAMP. Although CREB was served as a negative factor for the HIF-1 activity, it may not be a major PKA target in the cAMP-dependent HIF-alpha repression pathway. Induction of hypoxia responsive genes was suppressed by dibutyryl cAMP. Our results provide additional insight into a regulatory mechanism of hypoxic response.

引用

页码：839 / 844

页数：6

共 23 条

[1]

SEPT9_v1 Up-regulates Hypoxia-inducible Factor 1 by Preventing Its RACK1-mediated Degradation [J].