RUTHENIUM RED DELAYS THE ONSET OF CELL-DEATH DURING OXIDATIVE STRESS OF RAT HEPATOCYTES
RUTHENIUM RED DELAYS THE ONSET OF CELL-DEATH DURING OXIDATIVE STRESS OF RAT HEPATOCYTES
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DOI：
10.1016/0016-5085(92)90193-3
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发表时间：
1992-03-01
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：
GROSKREUTZ, JL;BRONK, SF;GORES, GJ
本实验用100μ/L的叔丁基氢过氧化氢诱导大鼠肝细胞产生氧化应激反应，以探讨钌红对大鼠肝细胞致死性氧化损伤的保护作用。氧化应激2小时后，细胞活力明显高于未加25μ的细胞活力(37%vs.4.6%；P<；0.01)。尽管有这种细胞保护作用，钌红并不改变谷胱甘肽耗竭、丙二醛生成或三磷酸腺苷耗竭的速度或程度。相反，钌红确实延缓了线粒体膜电位的丧失(30分钟内分别为78%和42%；P<；0.01)。然而，Ru红的保护作用不能完全通过保护线粒体膜电位来解释。事实上，在线粒体解偶联剂10μ摩尔/L羰基氰基氯苯肼(CCCP)作用2小时后，Ru红仍能提高细胞存活率(39%vs.13%；P<；0.01)。细胞内游离钙在线粒体解偶联过程中并未发生改变，提示不能用阻断线粒体钙转运来解释Ru红的细胞保护作用。在叔丁基氢过氧化氢(434±62vs.242±20nmol/106细胞；P=0.016)或CCCP(236±50nmol/106cell；99±38nmol/106细胞；P=0.04)作用2小时后，Ru红对蛋白质的降解有抑制作用。结果表明，Ru红可能通过抑制降解的蛋白水解酶活性来保护肝细胞免受损伤。提示蛋白降解可能是导致肝细胞致死性氧化损伤的重要机制。
Our objective was to determine if ruthenium red protects against lethal oxidative injury of rat hepatocytes.tert-Butyl hydroperoxide, 100 μmol/L, was used to produce oxidative stress. After 2 hours of oxidative stress, cell viability was greater with than without 25 μmol/L ruthenium red (37% vs. 4.6%;P< 0.01). Despite this cytoprotection, ruthenium red did not alter the rate or extent of glutathi one depletion, malondialdehyde generation, or adenosine triphosphate depletion. In contrast, ruthenium red did retard loss of the mitochondrial membrane potential (78% vs. 42% within 30 minutes;P< 0.01). However, the protective effect of ruthenium red could not solely be explained by preserving the mitochondrial membrane potential. Indeed, ruthenium red still improved cell survival after 2 hours of exposure to 10 μmol/L carbonyl cyanidem-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler (39% vs. 13%;P< 0.01). Cytosolic free calcium values did not change during the uncoupling of mitochondria, suggesting that the cytoprotective properties of ruthenium red cannot be explained by blocking mitochondrial calcium transport. Ruthenium red did inhibit proteolysis after 2 hours of exposure totert-butyl hydroperoxide (434 ± 62 vs. 242 ± 20 nmol/106cells;P= 0.016) or CCCP (236 ± 50 vs. 99 ± 38 nmol/106cells;P= 0.04). The results indicate that ruthenium red appears to protect against hepatocellular injury by inhibiting degradative proteolytic activity. It is concluded that proteolysis may be an important mechanism contributing to lethal oxidative injury of hepatocytes.