The effects of bromobenzene and carbon tetrachloride exposure in vitro on the phospholipase C activity of rat liver cells.
The effects of bromobenzene and carbon tetrachloride exposure in vitro on the phospholipase C activity of rat liver cells.
复制标题
溴苯和四氯化碳体外暴露对大鼠肝细胞磷脂酶C活性的影响。
DOI：
10.1016/0041-008x(82)90044-8
复制
发表时间：
1982
影响因子：
3.8
通讯作者：
Schwertz,DW
中科院分区：
文献类型：
--
作者：
Lamb,RG;Schwertz,DW
从分离的大鼠肝细胞中制备匀浆，该肝细胞预先在溴苯（BB）、四氯化碳（CCl 4）或二甲基亚砜（DMSO =对照溶剂）的存在下孵育（30至120分钟）。与暴露于DMSO的肝细胞相比，与BB和CCl 4孵育的肝细胞匀浆表现出将标记的膜结合磷脂酸转化为二酰甘油的能力迅速增加（2 - 5倍）。BB-和CCl 4-依赖性增加二酰基甘油（DG）的含量，在磷脂酸的费用，是Ca 2+依赖性和归因于细胞表面（质膜）酶活性的变化，因为响应主要发生在1000克细胞组分。当纯化的质膜或从新鲜肝匀浆中分离的1000 μ g细胞组分与BB和CCl 4在体外孵育时，也观察到标记的磷脂酸转化为DG的增加（2 - 4倍）。这些钙依赖性，BB-和四氯化碳诱导的肝细胞甘油脂含量的变化是由BB-和四氯化碳激活的磷脂酶C，降解膜磷脂。这一假设得到以下观察结果的支持：BB和CCl 4暴露（5分钟）后，肝细胞单层的32 P标记磷脂被迅速分解代谢（10 - 50%）。此外，有一个增加的转化[甲基-14 C]胞苷二磷酸胆碱磷脂酰胆碱后，细胞表面组分与磷脂酶C，BB，或四氯化碳孵育，这反映了肝细胞DG含量的上升的变化。BB和CCl 4诱导的肝细胞磷脂酶C活性快速升高（降解细胞磷脂）可能破坏膜的结构和功能，并可能代表毒性物质相关肝细胞损伤的早期事件。
Homogenates were prepared from isolated rat hepatocytes, previously incubated (30 to 120 min) in the presence of bromobenzene (BB), Carbon tetrachloride (CCl4), or dimethyl sulfoxide (DMSO = control vehicle). Homogenates of hepatocytes incubated with BB and CCl4compared to those exposed to DMSO exhibited a rapid increase (two- to five-fold) in their capacity to convert labeled, membrane-bound phosphatidic acid into diacylglycerol. The BB- and CCl4-dependent increase in diacylglycerol (DG) content, at the expense of phosphatidate, was Ca2+dependent and was attributed to changes in cell surface (plasma membrane) enzyme activity since the response occurred primarily in 1000g cell fractions. when either purified plasma membranes or 1000g cell fractions, isolated from fresh liver homogenates, were incubated with BB and CCl4in vitro, a rise (two- to fourfold) in the conversion of labeled phosphatidate into DG was also observed. These Ca2+-dependent, BB- and CCl4-induced changes in hepatocellular glycerolipid content were caused by a BB- and CCl4-activated phospholipase C which degrades membrane phospholipids. This hypothesis is supported by the observation that32P-labeled phospholipids of hepatocyte monolayers were rapidly catabolized (10 to 50%) after BB and CCl4exposure (5 min). Also, there was an increased conversion of [methyl-14C]cytidine diphosphocholine into phosphatidylcholine after cell surface fractions were incubated with phospholipase C, BB, or CCl4, a change which reflects a rise in hepatocellular DG content. A rapid, BB- and CCl4-induced rise in hepatocellular phospholipase C activity that degrades cellular phospholipids could disrupt the structure and function of membranes and may represent an early event in toxic substance-related hepatocyte injury.