SWELLING, REDUCTIVE STRESS, AND CELL-DEATH DURING CHEMICAL HYPOXIA IN HEPATOCYTES
SWELLING, REDUCTIVE STRESS, AND CELL-DEATH DURING CHEMICAL HYPOXIA IN HEPATOCYTES
复制标题
DOI：
10.1152/ajpcell.1989.257.2.c347
复制
发表时间：
1989-08-01
影响因子：
--
通讯作者：
LEMASTERS, JJ
中科院分区：
文献类型：
--
作者：
GORES, GJ;FLARSHEIM, CE;LEMASTERS, JJ
在大鼠肝细胞中，我们用 KCN 加碘乙酸检查了化学缺氧期间细胞体积、泡形成和细胞活力丧失之间的关系。在低渗介质（150-200 mosmol/kgH2O）中，化学缺氧期间细胞膨胀程度比在等渗介质中更大，但细胞杀伤率相同。添加到等渗培养基中的蔗糖 (300 mM) 可防止早期细胞肿胀，但实际上会加速细胞死亡。相比之下，甘露醇 (300 mM) 可以提高细胞存活率，但不能防止细胞肿胀。无论缓冲液张力如何，都会发生气泡形成。抗氧化剂是去铁胺和氰化醇，但不是超氧化物歧化酶.+-。过氧化氢酶延迟致死细胞损伤。与厌氧化学缺氧相比，有氧条件下的细胞杀伤力更大。使用二氯荧光素测定法测量氢过氧化物的形成，并且在有氧而非厌氧化学缺氧期间加速。结果表明细胞肿胀并不是气泡形成或致命细胞损伤的驱动力。我们得出的结论是，呼吸抑制引起的“还原应激”有利于有毒氧物质的形成，并可能在间歇性或不完全缺氧期间导致致命的细胞损伤。
In rat hepatocytes, we examined the relationship between cell volume, bleb formation, and loss of cell viability during chemical hypoxia with KCN plus iodoacetic acid. In hypotonic media (150-200 mosmol/kgH2O), cells swelled to a greater extent during chemical hypoxia than in isotonic media, but rates of cell killing were identical. Sucrose (300 mM) added to isotonic media prevented early cell swelling but actually accelerated cell killing. In contrast, mannitol (300 mM) improved cell survival but did not prevent cell swelling. Bleb formation occurred regardless of buffer tonicity. The antioxidants desferrioxamine and cyanidanol but not superoxide dismutase .+-. catalase delayed lethal cell injury. Cell killing was greater during aerobic compared with anaerobic chemical hypoxia. Hydroperoxide formation was measured using a dichlorofluorescin assay and was accelerated during aerobic but not anaerobic chemical hypoxia. The results indicate that cell swelling is not the driving force of bleb formation or lethal cell injury. We conclude that "reductive stress" caused by respiratory inhibition favors formation of toxic oxygen species and may contribute to lethal cell injury during intermittent or incomplete oxygen deprivation.