Regulatory role of ovarian sex hormones in calcium uptake activity of cardiac sarcoplasmic reticulum
Regulatory role of ovarian sex hormones in calcium uptake activity of cardiac sarcoplasmic reticulum
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DOI：
10.1152/ajpheart.00660.2005
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发表时间：
2006-09-01
影响因子：
4.8
通讯作者：
Wattanapermpool, Jonggonnee
中科院分区：
文献类型：
--
作者：
Bupha-Intr, Tepmanas;Wattanapermpool, Jonggonnee
心肌细胞内Ca 2+处理的改变可能是卵巢性剥夺条件下观察到的心功能不全的基础。为了验证卵巢性激素在心肌细胞内Ca ~（2+）动员中具有重要作用的假设，在10周去卵巢大鼠心脏中测定了肌浆网（SR）Ca ~（2+）摄取和SR Ca ~（2+）-ATP酶（SERCA）活性。使用左心室匀浆制剂，一个显着的抑制最大SR Ca 2+摄取活动，但增加SR Ca 2+的反应，证明在卵巢切除心脏。在从卵巢切除的心脏SR富集膜制剂中的SERCA活性的平行测量中，还检测到抑制的最大SERCA活性与pCa（-对数摩尔游离Ca 2+浓度）和SERCA活性之间的关系的显著偏移。观察到与抑制的最大SERCA活性相关的SERCA蛋白的显著下调和SERCA mRNA水平的降低。虽然总受磷蛋白和磷酸化Ser 16受磷蛋白水平没有变化，但发现磷酸化Thr（17）受磷蛋白减少，以及受磷蛋白化学计量的超抑制单体形式增加。雌激素和黄体酮补充剂在预防卵巢切除心脏变化方面同样有效。我们的数据首次表明，女性性激素在调节心脏SR Ca 2+摄取中发挥了重要作用。在酶缺乏的条件下，有一个适应性反应的SERCA逃避受磷蛋白的调节作用。
Alterations in the intracellular Ca2+ handling in cardiomyocytes may underlie the cardiac dysfunction observed in the ovarian sex hormone-deprived condition. To test the hypothesis that ovarian sex hormones had a significant role in the cardiac intracellular Ca2+ mobilization, the sarcoplasmic reticulum (SR) Ca2+ uptake and SR Ca2+-ATPase (SERCA) activity were determined in 10-wk ovariectomized rat hearts. With the use of left ventricular homogenate preparations, a significant suppression of maximum SR Ca2+ uptake activity, but with an increase in SR Ca2+ responsiveness, was demonstrated in ovariectomized hearts. In parallel measurements of SERCA activity in SR-enriched membrane preparations from ovariectomized hearts, a suppressed maximum SERCA activity with a leftward shift in the relationship between pCa (-log molar free Ca2+ concentration) and SERCA activity was also detected. A significant downregulation of SERCA proteins and reduction in the SERCA mRNA level were observed in association with suppressed maximum SERCA activity. While there were no changes in total phospholamban and phosphorylated Ser16 phospholamban levels, a decrease in phosphorylated Thr(17) phospholamban as well as an increase in the suprainhibitory, monomeric form of phospholamban stoichiometry was found. Estrogen and progesterone supplementations were equally effective in preventing changes in ovariectomized hearts. Our data showed for the first time that female sex hormones played an important role in the regulation of the cardiac SR Ca2+ uptake. Under hormone-deficient conditions, there was an adaptive response of SERCA that escaped the regulatory effect of phospholamban.