Sex differences in expression of calcium-handling proteins and beta-adrenergic receptors in rat heart ventricle
Sex differences in expression of calcium-handling proteins and beta-adrenergic receptors in rat heart ventricle
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DOI：
10.1016/j.lfs.2004.12.013
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发表时间：
2005-04-22
期刊：
影响因子：
6.1
通讯作者：
Schwertz, D
中科院分区：
文献类型：
--
作者：
Chu, SH;Sutherland, K;Schwertz, D
人体研究揭示了心肌功能以及心脏病发病率和表现的性别差异。肌细胞Ca 2+循环调节正常的收缩功能，而心力衰竭的心功能不全与Ca 2+处理蛋白的改变有关。β-肾上腺素能受体（β-AR）信号调节几种Ca 2+处理蛋白的活性，β-AR信号的改变与心脏病有关。本研究检测了雄性和雌性Sprague-Dawley大鼠健康心脏中β（1）-AR、β（2）-AR和Ca 2+处理蛋白表达的性别差异，这些蛋白包括：L型钙通道（Ca（v）1.2）、兰尼碱钙释放通道（RyR）、肌浆网Ca 2 + ATP酶（SERCA 2）、受磷蛋白（PLB）和Na+-Ca 2+交换蛋白（NCX）。使用Western印迹分析检测蛋白质水平。通过归一化为GAPDH mRNA丰度的真实的时间RT-PCR测定mRNA的减少。在存在和不存在异丙肾上腺素的情况下测量右心室乳头肌的收缩参数。结果表明，与男性相比，女性心室具有显著更高水平的Ca（v）1.2、RyR和NCX蛋白。RyR和NCX蛋白的信使RNA丰度在女性中显著较高，而Ca（v）1.2 mRNA在男性中较高。在β-AR、SERCA 2或PLB中未检测到差异。女性右乳头肌具有更快的最大力发展和下降速率（+/- dF/dt）。对异丙肾上腺素的反应无性别差异。结果显示，与dF/dt的小功能差异相关的关键心室Ca 2+处理蛋白的表达存在显著的性别差异。进一步的研究将确定这些关键蛋白质丰度的差异是否在心脏病发病率和表现的性别差异中发挥作用。(c)2005年爱思唯尔公司All rights reserved.
Human studies reveal sex differences in myocardial function as well as in the incidence and manifestation of heart disease. Myocellular Ca2+ cycling regulates normal contractile function; whereas cardiac dysfunction in heart failure has been associated with alterations in Ca2+-handling proteins. Beta-adrenergic receptor (beta-AR) signaling regulates activity of several Ca2+-handling proteins and alterations in beta-AR signaling are associated with heart disease. This study examines sex differences in expression of beta(1)-AR, beta(2)-AR, and Ca2+-handling proteins including: L-type calcium channel (Ca(v)1.2), ryanodine calcium-release channels (RyR), sarcoplasmic reticular Ca2+ ATPase (SERCA2), phospholamban (PLB) and Na+-Ca2+ exchange protein (NCX) in healthy hearts from male and female Sprague-Dawley rats. Protein levels were examined using Western blot analysis. Abundance of mRNA was determined by real time RT-PCR normalized to abundance of GAPDH mRNA. Contraction parameters were measured in right ventricular papillary muscle in the presence and absence of isoproterenol. Results demonstrate that female ventricle has significantly higher levels of Ca(v)1.2, RyR, and NCX protein compared to males. Messenger RNA abundance for RyR, and NCX protein was significantly higher in females whereas Ca(v)1.2 mRNA was higher in males. No differences were detected in beta-ARs, SERCA2 or PLB. Female right papillary muscle had a faster maximal rate of force development and decline (+/- dF/dt). There were no sex differences in response to isoproterenol. Results show significant sex differences in expression of key ventricular Ca2+-handling proteins that are associated with small functional differences in dF/dt. Further studies will determine whether differences in the abundance of these key proteins play a role in sex disparities in the incidence and manifestation of heart disease. (c) 2005 Elsevier Inc. All rights reserved.