Gender modulation of Ca2+ uptake in cardiac mitochondria
Gender modulation of Ca2+ uptake in cardiac mitochondria
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DOI：
10.1016/j.yjmcc.2004.04.023
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发表时间：
2004-08-01
影响因子：
5
通讯作者：
Schaefer, S
中科院分区：
文献类型：
--
作者：
Arieli, Y;Gursahani, H;Schaefer, S
背景：线粒体钙超载是界定缺血/再灌注损伤的重要因素。由于绝经前妇女相对免受缺血和心脏病的影响，我们测试了性别差异改变大鼠心脏线粒体Ca2+处理的假设。方法：使用从雄性、雌性和卵巢切除的Sprague-Dawley大鼠中分离的心脏线粒体，我们测量了暴露于钙丸时线粒体钙转运、氧化还原状态和膜电位（Deltapsi(m)）。用琥珀酸盐(S)或琥珀酸和丙酮酸盐（SP）作为底物调节氧化还原状态。结果：使用SP，底物条件导致较低的氧化还原状态（NADH/NAD'），女性线粒体的净Ca2+摄取率明显低于男性线粒体。使用环孢素A对线粒体过渡孔（MTP）的抑制表明，当雌性和卵巢切除动物的线粒体与雄性相比，两种底物溶液中的净Ca2+摄取显著降低，这一发现与线粒体单转运体的性别调节一致。钌红对Ca2+单转运体的阻断消除了钙释放的性别或底物溶液差异。虽然Ca2+添加后静息Deltapsi(m)和Deltapsi(m)没有显著差异，但80%的雌性样品从Ca2+诱导的去极化中恢复过来，而雄性和卵巢切除的动物分别为57%和43%。结论：女性心脏的线粒体在生理底物溶液（琥珀酸盐/丙酮酸盐）下具有较低的Ca2+摄取率，并且能够在高[Ca2+]条件下适当地维持Deltapsim。这些差异与Ca2+单转运蛋白的性别调节一致，可能是女性心肌缺血再灌注损伤较小的机制。(C) 2004年Elsevier Ltd.出版
Background: Mitochondrial calcium overload is an important factor in defining ischemia/reperfusion injury. Since pre-menopausal women are relatively protected from ischemia and heart disease, we tested the hypothesis that gender differences alter Ca2+ handling in rat cardiac mitochondria.Methods: Using cardiac mitochondria isolated from male, female, and ovariectornized Sprague-Dawley rats, we measured mitochondrial calcium transport, redox state, and membrane potential (Deltapsi(m)) during exposure to a calcium bolus. Redox state was modulated using either succinate (S) or succinate and pyruvate (SP) as substrates.Results: Net Ca2+ uptake rates were significantly lower in female than male mitochondria using SP, substrate conditions that resulted in a lower redox state (NADH/NAD'). Inhibition of the mitochondrial transition pore (MTP) using cyclosporin A showed significantly lower net Ca2+ uptake in both substrate solutions when mitochondria from female and ovariectornized animals were compared to males, a finding consistent with gender modulation of the mitochondrial uniporter. Blockade of the Ca2+ uniporter by ruthenium red abolished gender or substrate solution differences in calcium release. While there were no significant differences in resting Deltapsi(m) or Deltapsi(m) following Ca2+ addition, 80% of female samples recovered from Ca2+-induced depolarization compared to 57% and 43% of male and ovariectornized animals, respectively.Conclusions: Mitochondria from female hearts have lower Ca2+ uptake rates under physiologic substrate solutions (succinate/pyruvate) and are able to appropriately maintain Deltapsim under conditions of high [Ca2+]. These differences are consistent with gender modulation of the Ca2+ uniporter and may be a mechanism by which female myocardium, suffers less injury with ischemiaJreperfusion. (C) 2004 Published by Elsevier Ltd.