PGC-1α accelerates cytosolic Ca²⁺ clearance without disturbing Ca²⁺ homeostasis in cardiac myocytes

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• 作者：Min Chen ; Yanru Wang ; Aijuan Qu
• 关键词：PGC-1α ; Sarcoplasmic reticulum ; Calcium transient ; Calcium wave ; SERCA2a
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2010
• 出版时间：11 June 2010
• 年：2010
• 卷：396
• 期：4
• 页码：894-900
• 全文大小：680 K

文摘

Energy metabolism and Ca²⁺ handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1α in cardiac Ca²⁺ signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1α via adenoviral transduction. Our data shows that overexpressing PGC-1α improved myocyte contractility without increasing the amplitude of Ca²⁺ transients, suggesting that myofilament sensitivity to Ca²⁺ increased. Interestingly, the decay kinetics of global Ca²⁺ transients and Ca²⁺ waves accelerated in PGC-1α-expressing cells, but the decay rate of caffeine-elicited Ca²⁺ transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca²⁺-ATPase (SERCA2a), but not Na⁺/Ca²⁺ exchange (NCX) contribute to PGC-1α-induced cytosolic Ca²⁺ clearance. Furthermore, PGC-1α induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1α did not disturb cardiac Ca²⁺ homeostasis, because SR Ca²⁺ load and the propensity for Ca²⁺ waves remained unchanged. These data suggest that PGC-1α can ameliorate cardiac Ca²⁺ cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1α-calcium handing pathway sheds new light on the role of PGC-1α in the therapy of cardiac diseases.