Weinberg J M, Davis J A, Abarzua M, Kiani T
Department of Internal Medicine, Veterans Administration Medical Center Ann Arbor, MI.
J Lab Clin Med. 1989 May;113(5):612-22.
We designed studies to characterize metabolic aspects of the protective effects of glycine and glutathione against hypoxic proximal tubule cell injury b clarifying the relationship between protection and preservation of tubule cell adenosine triphosphate (ATP) and glutathione levels. The tubule preparation was glutatione depleted as isolated although some recovery occurred during incubation at 37 degrees C, and this recovery was enhanced by treatment with glutatione precursors. Increasing the duration of hypoxia from 30 minutes to 60 minutes produced increasingly extensive lethal tubule cell injury that was almost completely prevented, even at the 60-minute duration, by inclusion of either 2 mmol/L glutathione or 2 mmol/L glycine in the tubule incubation medium. Cell ATP levels decreased to the same extent and at the same rate in protected and unprotected hypoxic tubules. Glycine- and glutathione-protected tubules maintained higher cell glutathione levels than unprotected tubules at all durations of hypoxia studied. However, completely eliminating this increment of glutathione with either the gamma-glutamylcysteine synthetase inhibitor, buthionine sulfoximine, or the glutathione reductase inhibitor, 1,3-bis(2-chloroethyl)-1-nitrosourea, did not prevent protection. The data indicate that the striking protection against hypoxic injury to the isolated tubules provided by treatment with glycine or glutathione is independent of preservation of tubule cell ATP and glutathione levels, to the extent that difference of these levels can be discriminated in intact cells with present methods.
我们设计了一些研究，通过阐明保护作用与肾小管细胞三磷酸腺苷（ATP）及谷胱甘肽水平的维持之间的关系，来描述甘氨酸和谷胱甘肽对缺氧近端肾小管细胞损伤的保护作用的代谢方面。尽管在37℃孵育期间有一定程度的恢复，但分离的肾小管制剂中谷胱甘肽已被耗尽，而用谷胱甘肽前体处理可增强这种恢复。将缺氧时间从30分钟延长至60分钟会导致越来越广泛的致命性肾小管细胞损伤，而在肾小管孵育培养基中加入2 mmol/L谷胱甘肽或2 mmol/L甘氨酸，即使在60分钟的缺氧时间下，也几乎能完全防止这种损伤。在受保护和未受保护的缺氧肾小管中，细胞ATP水平以相同程度和相同速率下降。在所有研究的缺氧时间段内，甘氨酸和谷胱甘肽保护的肾小管细胞内谷胱甘肽水平均高于未受保护的肾小管。然而，用γ-谷氨酰半胱氨酸合成酶抑制剂丁硫氨酸亚砜胺或谷胱甘肽还原酶抑制剂1,3-双（2-氯乙基）-1-亚硝基脲完全消除谷胱甘肽的这种增加，并不会阻止保护作用。数据表明，用甘氨酸或谷胱甘肽处理对分离的肾小管缺氧损伤提供的显著保护作用，与肾小管细胞ATP和谷胱甘肽水平的维持无关，就目前方法在完整细胞中能够区分这些水平的差异而言。
