title: CoCl2-induced expression of p300 promotes neuronal-like PC12 cell damage.
abstract: 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.
authors.affiliation: Department of Pathophysiology and High Altitude Physiology, College of High Altitude Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiao Ling
authors.initials: XL
authors.lastname: Tan
authors.forename: Xiao Yong
authors.initials: XY
authors.lastname: Huang
authors.forename: Wen Xiang
authors.initials: WX
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zai
authors.forename: Qing Yuan
authors.initials: QY
authors.lastname: Huang
authors.forename: Yong Jun
authors.initials: YJ
authors.lastname: Luo
authors.forename: Yu Qi
authors.initials: YQ
authors.lastname: Gao
mesh_terms: 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*
chemical_list: 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