GLYCINE CYTOPROTECTION DURING LETHAL HEPATOCELLULAR INJURY FROM ADENOSINE-TRIPHOSPHATE DEPLETION
GLYCINE CYTOPROTECTION DURING LETHAL HEPATOCELLULAR INJURY FROM ADENOSINE-TRIPHOSPHATE DEPLETION
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DOI：
10.1016/0016-5085(92)90338-y
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发表时间：
1992-06-01
期刊：
影响因子：
29.4
通讯作者：
GORES, GJ
中科院分区：
文献类型：
--
作者：
DICKSON, RC;BRONK, SF;GORES, GJ
甘氨酸可保护肾小管细胞在三磷酸腺苷 (ATP) 耗尽期间免于细胞死亡。尽管肝脏在甘氨酸代谢中发挥着关键作用，但仍缺乏有关甘氨酸对致命性肝细胞损伤的影响的信息。因此，本研究的目的是确定甘氨酸在大鼠肝细胞 ATP 消耗期间的潜在细胞保护作用。使用 2.5 mmol/L 氰化钾 (KCN) 进行代谢抑制，以产生 ATP 消耗。用 KCN 处理的肝细胞悬液的 2 小时活力为 5.9% ± 2.0%，而在 2.0 mmol/L 甘氨酸存在下用 KCN 处理的细胞的活力为 80.2% ± 1.5%，与对照组几乎相同 (81.5% ± 1.9%)。甘氨酸的细胞保护作用具有剂量依赖性和氨基酸特异性。甘氨酸的细胞保护作用不是由蛋白质合成、甘氨酸线粒体代谢、胞质酸中毒或细胞内谷胱甘肽或 ATP 的保存介导的。然而，KCN 处理 1、2 和 3 小时后，甘氨酸确实使总细胞蛋白水解分别降低了 18% ± 2%、25% ± 3% 和 33% ± 1%（P < 0.01）。甘氨酸对蛋白水解的抑制与其细胞保护作用在相同范围内呈剂量依赖性。结果表明，甘氨酸通过抑制降解蛋白水解活性来防止肝细胞损伤。结论是，蛋白水解可能是 ATP 耗竭过程中导致肝细胞致命损伤的重要机制。
Glycine protects renal tubule cells from cell death during adenosine triphosphate (ATP) depletion. Although the liver plays a key role in glycine metabolism, information is lacking regarding the effects of glycine on lethal hepatocellular injury. Thus, the aim of this study was to determine the potential cytoprotective role of glycine during ATP depletion of rat hepatocytes. Metabolic inhibition with 2.5 mmol/L potassium cyanide (KCN) was used to produce ATP depletion. Hepatocyte suspensions treated with KCN had a 2-hour viability of 5.9% ± 2.0%, whereas cells treated with KCN in the presence of 2.0 mmol/L glycine had a viability of 80.2% ± 1.5%, which was virtually identical to controls (81.5% ± 1.9%). Glycine cytoprotection was dose dependent and amino acid specific. The cytoprotective effect of glycine was not mediated by protein synthesis, glycine mitochondrial metabolism, cytosolic acidosis, or preservation of either intracellular cellular glutathione or ATP. However, glycine did decrease total cellular proteolysis by 18% ± 2%, 25% ± 3%, and 33% ± 1% after 1, 2, and 3 hours of KCN treatment, respectively (P< 0.01). Inhibition of proteolysis by glycine was dose dependent over the same range as its cytoprotection. The results suggest that glycine protects against hepatocellular injury by inhibiting degradative proteolytic activity. It was concluded that proteolysis may be an important mechanism contributing to lethal injury of hepatocytes during ATP depletion.