Channelpedia

PubMed 22129453


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPC , TRPC1 , TRPC3 , TRPC6



Title: Mild hypoxia-induced cardiomyocyte hypertrophy via up-regulation of HIF-1α-mediated TRPC signalling.

Authors: Wenfeng Chu, Lin Wan, Dan Zhao, Xuefeng Qu, Fulai Cai, Rong Huo, Ning Wang, Jiuxin Zhu, Chun Zhang, Fangfang Zheng, Ruijun Cai, Deli Dong, Yanjie Lu, Baofeng Yang

Journal, date & volume: J. Cell. Mol. Med., 2012 Sep , 16, 2022-34

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22129453


Abstract
Hypoxia-inducible factor-1 alpha (HIF-1α) is a central transcriptional regulator of hypoxic response. The present study was designed to investigate the role of HIF-1α in mild hypoxia-induced cardiomyocytes hypertrophy and its underlying mechanism. Mild hypoxia (MH, 10% O(2)) caused hypertrophy in cultured neonatal rat cardiac myocytes, which was accompanied with increase of HIF-1α mRNA and accumulation of HIF-1α protein in nuclei. Transient receptor potential canonical (TRPC) channels including TRPC3 and TRPC6, except for TRPC1, were increased, and Ca(2+)-calcineurin signals were also enhanced in a time-dependent manner under MH condition. MH-induced cardiomyocytes hypertrophy, TRPC up-regulation and enhanced Ca(2+)-calcineurin signals were inhibited by an HIF-1α specific blocker, SC205346 (30 μM), whereas promoted by HIF-1α overexpression. Electrophysiological voltage-clamp demonstrated that DAG analogue, OAG (30 μM), induced TRPC current by as much as 170% in neonatal rat cardiomyocytes overexpressing HIF-1α compared to negative control. These results implicate that HIF-1α plays a key role in development of cardiac hypertrophy in responses to hypoxic stress. Its mechanism is associated with up-regulating TRPC3, TRPC6 expression, activating TRPC current and subsequently leading to enhanced Ca(2+)-calcineurin signals.