CoCl2-induced expression of p300 promotes neuronal-like PC12 cell damage.
Hypoxia inducible factor-1 (HIF-1) is an important transcription activator involved in cell responses to hypoxic stress. Previous studies demonstrated that HIF-1 exerts both pro- and anti-survival effects under hypoxia. The mechanisms underlying these contrary effects of HIF-1 remain unclear. Transcription co-activator p300 is necessary for HIF-1-induced transcriptional activation. Many factors inhibit HIF-1 activity by competitively binding to p300, which suggests that p300 is a key player in the modulation of HIF-1 function. To examine the alteration of p300 expression under hypoxia and its role in hypoxia-induced neuronal damage, neuronal-like PC12 cells were cultured with cobalt chloride (CoCl2), a hypoxia mimic reagent. The results showed that CoCl2 treatment-induced p300 expression along with an increase in cell damage. Furthermore, CoCl2-induced cell damage was attenuated by suppression of p300 expression with short hairpin RNA (shRNA). The data suggests that CoCl2-induced up-regulation of p300 expression promotes neuronal-like PC12 cell damage.
Tan
Xiao Ling
XL
Department of Pathophysiology and High Altitude Physiology, College of High Altitude Medicine, Third Military Medical University, Chongqing 400038, China.
Huang
Xiao Yong
XY
Gao
Wen Xiang
WX
Zai
Yu
Y
Huang
Qing Yuan
QY
Luo
Yong Jun
YJ
Gao
Yu Qi
YQ
D000818:Animals; D016587:Antimutagenic Agents / Q000633:toxicity; D003035:Cobalt / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D002534:Hypoxia, Brain / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D016716:PC12 Cells; D012313:RNA / Q000235:genetics / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*
D016587:Antimutagenic Agents; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003035:Cobalt; D012313:RNA; D050880:p300-CBP Transcription Factors; C018021:cobaltous chloride