Destruction of liver microsomal calcium pump activity by carbon tetrachloride and bromotrichloromethane.
Destruction of liver microsomal calcium pump activity by carbon tetrachloride and bromotrichloromethane.
复制标题
四氯化碳和三氯溴甲烷破坏肝微粒体钙泵活性。
DOI：
10.1016/0006-2952(81)90184-2
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发表时间：
1981
影响因子：
5.8
通讯作者：
Recknagel,RO
中科院分区：
文献类型：
--
作者：
Lowrey,K;GlendeJr,EA;Recknagel,RO
在四氯化碳（CCl4）中毒期间，观察到细胞钙稳态紊乱，钙含量在给药后8小时发生大量改变。Mooreel。[10]研究表明，大鼠肝光滑内质网具有固钙功能，但这种能力在给药后30分钟内严重下降。提示内质网钙泵活性紊乱可能在ccl4肝毒性表达中起关键作用。研究了溴三氯甲烷（BrCCl3）和ccl4代谢对无Fe2+大鼠肝微粒体钙泵的影响。结果表明，钙摄取的严重缺陷与这些药物诱导的最小脂质过氧化有关。在一定的脂质过氧化水平下，钙摄取比微粒体酶葡萄糖-6-磷酸酶和氨基吡啶去甲基酶的活性受到更严重的影响。在钙固存测定之前，在孵育过程中，5毫米ATP的存在使钙摄取增加了7倍。BrCCl3-NADPH诱导的脂质过氧化伴随着钙负载微粒体的钙泄漏。这些结果加强了细胞内钙稳态紊乱可能是brccl3和CCl4诱导肝损伤的关键事件的可能性。
Disturbed cellular calcium homeostatis has been observed during carbon tetrachloride (CCl4) poisoning, with large alterations in calcium content occurring 8 hr after administration. Mooreel at. [10] have shown that the hepatic smooth endoplasmic reticulum can sequester calcium and that this ability is decreased severely within 30 min after CCl4administration to rats. It was suggested that disturbed endoplasmic reticulum calcium pump activity may have a critical role in the expression of CCl4hepatotoxicity. We examined the effect of bromotrichloromethane (BrCCl3) and CCl4metabolism on the calcium pump of Fe2+-free rat liver microsomes. It was determined that severe deficits in calcium uptake can be correlated with minimal lipid peroxidation induced by these agents. At a given level of lipid peroxidation, calcium uptake was affected more severely than were the activities of the microsomal enzymes glucose-6-phosphatase and aminopyrine demethylase. Calcium uptake was increased 7-fold by the presence of 5 mM ATP in incubations prior to assay of calcium sequestration. Lipid peroxidation induced by BrCCl3-NADPH was accompanied by leakage of calcium from calcium-loaded microsomes. These results strengthen the possibility that disturbances in intracellular calcium homeostasis may be a key event in liver injury induced by BrCCl3and CCl4.