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Silencing TRPM7 promotes growth/proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway

牛老师添加于 2015-5-12 19:53 | 1663 次阅读 | 0 个评论

作者
Inoue K, Xiong Z-G
摘要
AIMS: The presence and potential function of transient receptor potential melastatin 7 (TRPM7), a Ca2+-permeable non-selective cation channel of the TRP channel superfamily in human vascular endothelial cells, were examined. METHODS AND RESULTS: Whole-cell patch-clamp recordings showed outward-rectifying currents in human umbilical vein endothelial cells (HUVECs), which was potentiated by removing the extracellular Ca2+ and Mg2+, but inhibited by non-specific TRPM7 blocker Gd3+ or 2-aminoethoxydiphenyl borate (2-APB). TRPM7 mRNA was detected in HUVECs by RT-PCR, but TRPM6, its closest homologue, was not. Silencing TRPM7 by small interfering RNA (siRNA) decreased the level of TRPM7 mRNA and the TRPM7-like current. Interestingly, knockdown of TRPM7 with siRNA or inhibition of TRPM7 function with 2-APB increased the phosphorylation of extracellular signal-regulated kinase (ERK) and enhanced growth/proliferation of HUVECs. This enhanced cell growth/proliferation was abolished by an inhibitor of the ERK signalling pathway. In addition to cell growth/proliferation, silencing TRPM7 also increased expression of nitric oxide synthase and nitric oxide production in an ERK pathway-dependent manner. CONCLUSION: These observations suggest that TRPM7 channels may play an important role in the function of vascular endothelial cells.
详细资料
- 关键词: Boron Compounds/pharmacology; Butadienes/pharmacology; Calcium/metabolism; *Cell Proliferation/drug effects; Cells, Cultured; Endothelial Cells/drug effects/*enzymology; Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/*metabolism; Humans; *MAP Kinase Signaling System/drug effects; Magnesium/metabolism; Membrane Potentials; Membrane Transport Modulators/pharmacology; Nitric Oxide/*metabolism; Nitric Oxide Synthase Type III/metabolism; Nitriles/pharmacology; Patch-Clamp Techniq ...
- 文献种类: Journal Article
- 期刊名称: Cardiovascular Research
- 期刊缩写: Cardiovasc Res
- 期卷页: 2009年第83卷第3期 547-557页
- 地址: Robert S. Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Ave. Portland, OR 97232, USA
- ISBN: 0008-6363
学科领域生物医药 » 基础医学
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