Mild hypoxia-induced cardiomyocyte hypertrophy via up-regulation of HIF-1α-mediated TRPC signalling.
Mild hypoxia-induced cardiomyocyte hypertrophy via up-regulation of HIF-1α-mediated TRPC signalling.
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DOI：
10.1111/j.1582-4934.2011.01497.x
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发表时间：
2012-09
影响因子：
5.3
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Chu W;Wan L;Zhao D;Qu X;Cai F;Huo R;Wang N;Zhu J;Zhang C;Zheng F;Cai R;Dong D;Lu Y;Yang B
缺氧诱导因子-1 α（HIF-1α）是缺氧反应的核心转录调节因子。本研究旨在探讨缺氧诱导因子-1 α（HIF-1α）在轻度缺氧诱导的心肌细胞肥大中的作用及其机制。轻度缺氧（MH，10%O2）可引起培养乳鼠心肌细胞肥大，并伴有HIF-1α mRNA表达增加和HIF-1α蛋白在细胞核内聚集。瞬时受体电位经典（TRPC）通道，包括TRPC 3和TRPC 6，除TRPC 1外，在MH条件下增加，Ca 2 +-calcineurin信号也以时间依赖的方式增强。HIF-1α特异性阻断剂SC205346（30 μM）可抑制MH诱导的心肌细胞肥大、TRPC上调和Ca 2 +-calcineurin信号增强，而HIF-1α过表达则可促进上述作用。电生理电压钳实验表明，与阴性对照相比，DAG类似物OAG（30 μM）在过表达HIF-1α的乳鼠心肌细胞中诱导的TRPC电流增加了170%。这些结果提示HIF-1α在缺氧应激引起的心肌肥厚中起着关键作用。其机制与上调TRPC 3、TRPC 6表达，激活TRPC电流，导致Ca 2 +-calcineurin信号增强有关。
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% O2) 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 Ca2+-calcineurin signals were also enhanced in a time-dependent manner under MH condition. MH-induced cardiomyocytes hypertrophy, TRPC up-regulation and enhanced Ca2+-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 Ca2+-calcineurin signals.
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影响因子：
--
作者：
Lin, Sze-Kwan;Shun, Chia-Tung;Liu, Chia-Ming
通讯作者：
Liu, Chia-Ming
DOI：
10.1073/pnas.0808801106
发表时间：
2009-02-17
影响因子：
11.1
作者：
O'Hagan, Kathleen A.;Cocchiglia, Sinead;Allan, Bernard B.
通讯作者：
Allan, Bernard B.
DOI：
10.1152/ajpheart.00796.2008
发表时间：
2009-03-01
影响因子：
4.8
作者：
Sharikabad, Mohammad Nouri;Aronsen, Jan Magnus;Brors, Odd
通讯作者：
Brors, Odd
影响因子：
3.7
作者：
Gutte, Henrik;Oxbol, Jytte;Kjaer, Andreas
通讯作者：
Kjaer, Andreas
DOI：
10.1002/cyto.990170205
发表时间：
1994-10-01
期刊：
CYTOMETRY
影响因子：
--
作者：
NOVAK, EJ;RABINOVITCH, PS
通讯作者：
RABINOVITCH, PS