The effects of androgens on calcium homeostasis in card*

雄激素对卡中钙稳态的影响*

• 批准号: 6526772
• 负责人: KISH L GOLDEN
• 金额: $ 12.11万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-08 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6526772
• 关键词: adenosinetriphosphatase; androgens; calcium flux; cardiovascular disorder; hormone regulation /control mechanism; laboratory rat; messenger RNA; muscle cells; muscle contraction; myocardium; myosins; pathologic process; protein isoforms; voltage /patch clamp

DESCRIPTION (Applicant?s abstract) Aging is associated with a decline in circulating androgens and this corresponds to the onset of cardiac abnormalities including a decline in myocardial contractility in men. Our overlying hypothesis is that a reduction in androgens influences myosin heavy chain composition and calcium homeostasis in cardiac myocytes. Specific aim 1 will test the hypothesis that androgen reduction in gonadectomized animals produces altered calcium transients and depressed contractility of freshly dissociated cardiac myocytes. Specific aim 2 will test the hypothesis that a decrease in circulating androgens results in reduced mRNA and protein abundance for the calcium regulating proteins and a decline in the ratio of MHC-alpha to MHC-beta. The third specific aim will test the hypothesis that androgen treatment of cardiac myocytes in vitro reduces the ration of MHC-alpha to MHC-beta and increases mRNA and protein levels for the major Ca2+ regulatory proteins. Biophysical assessment of E-C coupling will be carried out in ventricular myocytes isolated from normal and castrated rats treated with and without androgens. Whole cell voltage clamp recordings, video edge-detection and Ca2+ fluorescence measurements will be used to compare calcium channels, Na/Ca exchange and to analyze sarco(endo)plasmic reticulum ATPase function. The abundance of myosin isoforms, mRNA and proteins for the calcium homeostatic proteins will be compared using standard molecular and cellular approaches. Taken together these experiments will allow us to ascertain whether the expression and function of calcium regulating proteins and myosin isoforms are regulated by androgens. The results of these experiments will shed light into the role of androgens in regulating cardiac contractile function.

描述（申请人的摘要）衰老与循环下降有关 雄激素和这对应于心脏异常的发作 男性心肌收缩性的下降。我们上覆的假设是 雄激素的减少会影响肌球蛋白重链组成和 心肌细胞中的钙稳态。特定目标1将测试 假设雄激素减少雌激素会产生改变 钙瞬态和新鲜分离心脏的收缩性降低 心肌细胞。特定目标2将检验以下假设 循环雄激素导致mRNA和蛋白质丰度降低 调节蛋白质的钙和MHC-Alpha与MHC-β的比率下降。 第三个特定目的将检验雄激素治疗的假设 体外心肌细胞的体外，将MHC-Alpha的评分降低到MHC-beta和 提高主要Ca2+调节蛋白的mRNA和蛋白水平。 E-C耦合的生物物理评估将在心室进行 从正常和cast割的大鼠分离出的心肌细胞 雄激素。全电池电压夹记录，视频边缘检测和CA2+ 荧光测量将用于比较钙通道Na/ca 交换并分析SARCO（ENDO）等离子网动ATPase功能。这 钙稳态的肌球蛋白同工型，mRNA和蛋白质的丰度 将使用标准分子和细胞方法比较蛋白质。 综合这些实验将使我们能够确定 调节钙的蛋白质和肌球蛋白同工型的表达和功能是 由雄激素调节。这些实验的结果将浮出水面 雄激素在调节心脏收缩功能中的作用。