Katsumata T, Murata T, Yamaguchi M
Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, Shizuoka City, Japan.
Mol Cell Biochem. 1998 Aug;185(1-2):153-9. doi: 10.1023/a:1006803610945.
The alteration in calcium transport in the liver nuclei of rats orally administered carbon tetrachloride (CCl4) was investigated. Rats received a single oral administration of CCl4 (5, 10, and 25%, 1.0 ml/100 g body weight), and 5, 24 and 48 h later the animals were sacrificed. The administration of CCl4 (25%) caused a remarkable elevation of calcium content in the liver tissues and the nuclei of rats. Liver nuclear Ca2+-ATPase activity was markedly decreased by CCl4 (25%) administration. The presence of dibutyryl cyclic AMP(10(-4) and 10(-3) M) or inositol 1,4,5-trisphosphate (10(-6) and 10(-5) M) in the enzyme reaction mixture caused a significant decrease in Ca2+-ATPase activity in the liver nuclei obtained from normal rat, while the enzyme activity was significantly increased by calmodulin (1.0 and 2.0 microg/ml). These signaling factor's effects were completely impaired in the liver nuclei obtained from CCl4 (25%)-administered rats. DNA fragmentation in the liver nuclei obtained from CCl4-administered rats was significantly decreased by the presence of EGTA (2 mM) in the reaction mixture, suggesting that the endogenous calcium activates nuclear DNA fragmentation. The present study demonstrates that calcium transport system in the liver nuclei is impaired by liver injury with CCl4 administration in rats.
研究了口服四氯化碳(CCl4)的大鼠肝细胞核中钙转运的变化。大鼠单次口服CCl4(5%、10%和25%,1.0 ml/100 g体重),5、24和48小时后处死动物。给予CCl4(25%)导致大鼠肝脏组织和细胞核中的钙含量显著升高。给予CCl4(25%)可使肝细胞核Ca2+-ATP酶活性显著降低。酶反应混合物中存在二丁酰环磷酸腺苷(10^-4和10^-3 M)或肌醇1,4,5-三磷酸(10^-6和10^-5 M)会导致正常大鼠肝细胞核中Ca2+-ATP酶活性显著降低,而钙调蛋白(1.0和2.0 μg/ml)可使酶活性显著升高。在给予CCl4(25%)的大鼠获得的肝细胞核中,这些信号因子的作用完全受损。反应混合物中存在EGTA(2 mM)可显著降低给予CCl4的大鼠肝细胞核中的DNA片段化,表明内源性钙激活核DNA片段化。本研究表明,给予CCl4导致大鼠肝损伤会损害肝细胞核中的钙转运系统。