Lucas-Heron B, Le Ray B, Schmitt N
Laboratoire de Physiologie, Faculté de Médecine, Nantes, France.
FEBS Lett. 1995 Nov 6;374(3):309-11. doi: 10.1016/0014-5793(95)01122-u.
The effect of the myotoxic drug chlorpromazine was studied in vitro on proteins of sarcoplasmic reticulum and mitochondrial matrix of skeletal muscle in the normal mouse. Our results indicate that the drug is specific for calcium-binding proteins (calcium ATPase, calsequestrin and calmitine). Its proteolytic effect on these proteins, apparently due to the stimulation of specific proteases, could account for its myotoxic action. Moreover, calsequestrin (sarcoplasmic reticulum) and calmitine (mitochondrial matrix) were not sensitive to the same proteases. Proteases acting on calmitine were inhibited by alpha 2-macroglobulin but not those acting on calsequestrin. Despite some similarities between these two proteins, their characteristics of localization and sensitivity of their proteases indicate that calmitine has a specificity within the mitochondrial matrix and very probably plays a major role in the mitochondrial regulation of free calcium, which controls the activity of various enzymes of the mitochondrial matrix involved in ATP synthesis.
在体外研究了肌毒性药物氯丙嗪对正常小鼠骨骼肌肌浆网和线粒体基质蛋白质的影响。我们的结果表明，该药物对钙结合蛋白（钙ATP酶、肌集钙蛋白和钙调素）具有特异性。其对这些蛋白质的蛋白水解作用显然是由于特定蛋白酶的刺激，这可以解释其肌毒性作用。此外，肌集钙蛋白（肌浆网）和钙调素（线粒体基质）对相同的蛋白酶不敏感。作用于钙调素的蛋白酶被α2-巨球蛋白抑制，但作用于肌集钙蛋白的蛋白酶则不受抑制。尽管这两种蛋白质之间存在一些相似之处，但它们的定位特征和蛋白酶敏感性表明，钙调素在线粒体基质中具有特异性，很可能在控制参与ATP合成的线粒体基质各种酶活性的线粒体游离钙调节中起主要作用。
