TRPM7参与AngⅡ对心肌细胞镁离子平衡的调节-东南大学学报医学版

TRPM7参与AngⅡ对心肌细胞镁离子平衡的调节

单位：南通大学医学院病理学与病理生理学系, 江苏南通 226001

分类号：R36

出版年·卷·期（页码）：2014·33·第四期（445-449）

摘要：

目的：探讨TRPM7在血管紧张素Ⅱ（AngⅡ）对心肌细胞镁离子平衡调节中的作用。方法：采用原代培养的小鼠心肌细胞作为研究对象，实验分对照、AngⅡ、AngⅡ+氯沙坦（Losartan，AngⅡ的Ⅰ型受体阻断剂）及AngⅡ+2-APB（TRPM7通道阻断剂）组。实验试剂直接加入培养液中与细胞共孵育，应用mag-fura-2镁离子荧光探针动态检测心肌细胞内镁离子水平的变化，实时定量 PCR（qPCR）和Western Blotting检测TRPM7在原代培养心肌细胞中的表达水平。结果：与对照组相比，AngⅡ组心肌细胞胞内游离镁离子水平在细胞外生理镁离子浓度及高镁离子浓度环境下均有显著下降；应用Losartan或2-APB均可显著降低AngⅡ所致的游离镁离子下降的作用。qPCR和Western Blotting检测结果提示，AngⅡ对原代培养心肌细胞中TRPM7的表达水平无影响。结论：AngⅡ可通过Ⅰ型受体对原代培养心肌细胞的镁离子代谢产生显著影响，其机制可能是AngⅡ增强了心肌细胞TRPM7的功能而不影响其表达水平。

Objective: The aim of this study is to investigate the role of TRPM7 in magnesium homeostasis in cardiomyocytes regulated by AngⅡ. Methods: Primary cultured mouse neonatal cardiomyocytes were used for this study.Cell cultures were divided into control,AngⅡ,AngⅡ+Losartan and AngⅡ+2-APB groups.Testing agents were added into culture median and co-incubated with cells.Intracellular free magnesium levels were monitored with a magnesium selective fluorescent dye mag-fura-2.Real time quantitative PCR (qPCR) and Western Blotting were used for estimating the expression of TRPM7.Results: Comparing to the control group, intracellular magnesium levels was significantly decreased in AngⅡ group when physiological and high magnesium were present in the extracellular solution. Both losartan or 2-APB significantly reduced the role of decrease of intracellular magnesium levels caused by AngⅡ. Further studies with qPCR and Western Blotting indicated that the expression levels of TRPM7 were not affected by AngⅡ in cultured cardiomyocytes. Conclusion: AngⅡ significantly affected intracellular magnesium homeostasis in primary cultured cardiomyocytes via its AT1 receptor.The underlying mechanism is AngⅡ can enhance the function of TRPM7 with no effects on expression.

参考文献：

[1] SAH R,MESIRCA P,MASON X,et al.Timing of myocardial trpm7 deletion during cardiogenesis variably disrupts adult ventricular function,conduction,and repolarization[J].Circulation,2013,128(2):101-114.
[2] SHI J,ZHANG L,ZHANG Y W,et al.Downregulation of doxorubicin-induced myocardial apoptosis accompanies postnatal heart maturation[J].Am J Physiol Heart Circ Physiol, 2012,302(8):H1603-1613.
[3] BUNKENBURG B,van AMELSVOORT T,ROGG H,et al.Receptor-mediated effects of angiotensin Ⅱ on growth of vascular smooth muscle cells from spontaneously hypertensive rats[J].Hypertension,1992,20(6):746-754.
[4] NAKAGAMI H,TAKEMOTO M,LIAO J K.NADPH oxidase-derived superoxide anion mediates angiotensin Ⅱ-induced cardiac hypertrophy[J].J Mol Cell Cardiol,2003,35(7):851-859.
[5] YOGI A,CALLERA G E,ANTUNES T T,et al.Transient receptor potential melastatin 7 (TRPM7) cation channels,magnesium and the vascular system in hypertension[J].Circ J,2011,75(2):237-245.
[6] TOUYZ R M,HE Y,MONTEZANO A C,et al.Differential regulation of transient receptor potential melastatin 6 and 7 cation channels by ANG Ⅱ in vascular smooth muscle cells from spontaneously hypertensive rats[J].Am J Physiol Regul Integr Comp Physiol,2006,290(1):R73-78.
[7] AKAZAWA H,KOMURO I.Angiotensin Ⅱ type 1 and type 2 receptor[J].Nihon Rinsho,2009,67(4):687-694.
[8] ZHOU J,XU X,LIU J J,et al.AngiotensinⅡtype 2 receptors participate in the regulation of inflammatory cytokine secretion in adult rat hypertrophied cardiomyocytes[J].Nan Fang Yi Ke Da Xue Xue Bao,2008,28(11):1971-1973.
[9] TAKEZAWA R,SCHMITZ C,DEMEUSE P,et al.Receptor-mediated regulation of the TRPM7 channel through its endogenous protein kinase domain[J].Proc Natl Acad Sci USA,2004,101(16):6009-6014.

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