The role of Ca2+ in muscle cell damage
The role of Ca2+ in muscle cell damage
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DOI：
10.1196/annals.1363.013
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发表时间：
2005-01-01
期刊：
影响因子：
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通讯作者：
Gissel, Hanne
中科院分区：
文献类型：
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作者：
Gissel, Hanne
骨骼肌是人体最大的单一器官。骨骼肌损伤可能导致肌肉功能丧失，并且由于细胞内成分泄漏到循环中，广泛的肌肉损伤可能具有严重的全身性影响。Ca2+在所有肌肉中作为第二信使，可以激活从收缩激活到肌肉细胞降解的整个过程。因此，肌细胞控制胞质中的[Ca 2 +]（[Ca 2 +]（c））至关重要。如果肌膜对Ca2+的渗透性增加，则肌细胞可能遭受Ca2+过载，定义为无法控制[Ca2+]c。这可能导致钙蛋白酶的激活，导致细胞成分的蛋白水解，磷脂酶A（2）（PLA（2））的激活，影响膜完整性，活性氧（ROS）的产生增加，引起脂质过氧化，并可能导致线粒体Ca2+过载，所有这些都可能进一步恶化自我增强过程中的损伤。导致肌肉中Ca2+过载的Ca2+内流增加可能发生在一系列情况下，例如运动、机械和电创伤、长时间缺血、杜氏肌营养不良和恶病质。对抗剂包括膜稳定剂、Ca2+通道阻断剂、钙蛋白酶抑制剂、PLA2抑制剂和ROS清除剂。
Skeletal muscle is the largest single organ of the body. Skeletal muscle damage may lead to loss of muscle function, and widespread muscle damage may have serious systemic implications due to leakage of intracellular constituents to the circulation. Ca2+ acts as a second messenger in all muscle and may activate a whole range of processes ranging from activation of contraction to degradation of the muscle cell. It is therefore of vital importance for the muscle cell to control [Ca2+] in the cytoplasm ([Ca2+](c)). If the permeability of the sarcolemma for Ca2+ is increased, the muscle cell may suffer Ca2+ overload, defined as an inability to control [Ca2+]c. This could lead to the activation of calpains, resulting in proteolysis of cellular constituents, activation of phospholipase A(2) (PLA(2)), affecting membrane integrity, an increased production of reactive oxygen species (ROS), causing lipid peroxidation, and possibly mitochondrial Ca2+ overload, all of which may further worsen the damage in a selfreinforcing process. An increased influx of Ca2+ leading to Ca2+ overload in muscle may occur in a range of situations such as exercise, mechanical and electrical trauma, prolonged ischemia, Duchenne muscular dystrophy, and cachexia. Counteractions include membrane stabilizing agents, Ca2+ channel blockers, calpain inhibitors, PLA2 inhibitors, and ROS scavengers.