MITOCHONDRIAL DAMAGE IN MUSCLE OCCURS AFTER MARKED DEPLETION OF GLUTATHIONE AND IS PREVENTED BY GIVING GLUTATHIONE MONOESTER
MITOCHONDRIAL DAMAGE IN MUSCLE OCCURS AFTER MARKED DEPLETION OF GLUTATHIONE AND IS PREVENTED BY GIVING GLUTATHIONE MONOESTER
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DOI：
10.1073/pnas.86.2.471
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发表时间：
1989-01-01
影响因子：
11.1
通讯作者：
MEISTER, A
中科院分区：
文献类型：
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作者：
MARTENSSON, J;MEISTER, A
在通过向小鼠施用丁硫丙磺酰亚胺（一种γ-谷氨酰胺的不可逆抑制剂）产生的谷胱甘肽显著耗尽后，发现了与线粒体损伤相关的骨骼肌变性。谷氨酰半胱氨酸合成酶心肌线粒体未见损伤。这些研究表明，在不存在施加的应激（例如局部缺血、药物毒性）的情况下，非常显著的消耗（至约100%），3%）的谷胱甘肽必须发生在骨骼肌线粒体受到影响之前，因此表明肌肉具有大量过量的谷胱甘肽。骨骼肌和心脏谷胱甘肽的消耗呈双相模式，可能反映了线粒体谷胱甘肽的缓慢损失。当谷胱甘肽单异丙酯与丁硫丙啶亚砜亚胺一起给药时，没有发生骨骼肌变性;但是，当谷胱甘肽与丁硫丙啶亚砜亚胺一起给药时，确实发生了骨骼肌变性。谷胱甘肽单酯（而不是谷胱甘肽）的管理，防止了骨骼肌中的丁硫氨酸亚砜产生的线粒体谷胱甘肽的显着下降，并增加了心脏线粒体中的谷胱甘肽水平的值高于对照组。研究结果表明，谷胱甘肽单酯可能是有用的代理人保护心脏和骨骼肌对毒性。
Skeletal muscle degeneration associated with mitochondrial damage was found after marked depletion of glutathione produced by administration to mice of buthionine sulfoximine, an irreversible inhibitor of .gamma.-glutamylcystein synthetase. No mitochondrial damage was found in heart. These studies show that in the absence of applied stress (such as ischemia, drug toxicity), very marked depletion (to .apprxeq. 3% of the controls) of glutathione must occur before skeletal muscle mitochondria are affected and thus suggest that muscle has a large excess of glutathione. Depletion of glutathione followed a biphasic pattern in skeletal muscle and heart, probably reflecting, in the slow phase, loss of glutathione from mitochondria. Skeletal muscle degeneration did not occur when glutathione monoisopropyl ester was given together with buthionine sulfoximine; it did occur, however, when glutathione was given together with buthionine sulfoximine. Administration of the glutathione monoester (but not of glutathione) prevented the marked decline of mitochondrial glutathione produced by buthionine sulfoximine in skeletal muscle and increased the level of glutathione in heart mitochondria to values higher than the controls. The findings suggest that glutathione monoesters may be useful agents for protection of heart and skeletal muscle against toxicity.