Effects of chlorpyrifos on non-cholinergic toxicity endpoints in immortalized and primary rat hepatocytes under normal and hepatosteatotic conditions.
Effects of chlorpyrifos on non-cholinergic toxicity endpoints in immortalized and primary rat hepatocytes under normal and hepatosteatotic conditions.
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DOI：
10.1016/j.tiv.2022.105329
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Howell GE 3rd
中科院分区：
文献类型：
--
作者：
Kondakala S;Henein L;McDevitt E;Ross MK;Howell GE 3rd
毒死蜱(CPS)是使用最广泛的有机磷杀虫剂。OPs的非胆碱能靶标包括属于丝氨酸水解酶家族的酶。羧酸酯酶(CEs)参与外源物质的解毒和肝脏的脂质代谢。单甘油脂肪酶(MAGL)和脂肪酸酰胺水解酶(FAAH)是内源性大麻素的水解酶，也可被OP类化合物抑制。然而，在脂肪变性的肝脏中，没有体外研究检测这些非胆碱能终点对CPS暴露的敏感性。因此，我们测定了CPS在正常和脂肪变性条件下对永生化McArdle-RH7777(MCA)肝癌细胞和原代大鼠肝细胞中这些终点的影响。在最低浓度的CPS作用下，CES活性比MAGL或FAAH活性对抑制更敏感。此外，脂肪变性原代肝细胞的CES和MAGL活性对CPS介导的抑制作用的敏感性低于正常原代肝细胞，而CES抑制作用在脂肪变性的MCA细胞中更为明显。这些发现表明，脂肪变性条件以酶和细胞类型特异性的方式加强了暴露于CPS后对肝脏丝氨酸水解酶的抑制。CPS介导的这些酶的抑制可能在OP暴露后肝脏脂质代谢的改变中起一定作用。
Chlorpyrifos (CPS) is the most widely used organophosphate (OP) insecticide. Non-cholinergic targets of OPs include enzymes belonging to the serine hydrolase family. Carboxylesterases (Ces) are involved in detoxication of xenobiotics as well as lipid metabolism in the liver. Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are responsible for hydrolyzing endocannabinoids and can also be inhibited by OP compounds. However, there are no in vitro studies examining the sensitivities of these non-cholinergic endpoints following CPS exposure in the steatotic liver. Therefore, we determined the effects of CPS on these endpoints in immortalized McArdle-RH7777 (MCA) hepatoma cells and primary rat hepatocytes under normal and steatotic conditions. Ces activity was more sensitive to inhibition than MAGL or FAAH activity following exposure to the lowest CPS concentration. Additionally, Ces and MAGL activities in steatotic primary hepatocytes were less sensitive to CPS mediated inhibition than those in normal primary hepatocytes, whereas Ces inhibition was more pronounced in steatotic MCA cells. These findings suggest that steatotic conditions enhance the inhibition of hepatic serine hydrolases following exposure to CPS in an enzyme- and cell type-specific manner. CPS-mediated inhibition of these enzymes may play a part in the alterations of hepatic lipid metabolism following OP exposures.
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影响因子：
15.9
作者：
Osei-Hyiaman, D;DePetrillo, M;Kunos, G
通讯作者：
Kunos, G
影响因子：
14.8
作者：
Nomura, Daniel K.;Blankman, Jacqueline L.;Casida, John E.
通讯作者：
Casida, John E.
影响因子：
4.5
作者：
Howell GE 3rd;McDevitt E;Henein L;Mulligan C;Young D
通讯作者：
Young D
影响因子：
--
作者：
Blankman, Jacqueline L.;Simon, Gabriel M.;Cravatt, Benjamin F.
通讯作者：
Cravatt, Benjamin F.
影响因子：
3.8
作者：
Kondakala, Sandeep;Lee, Jung Hwa;Howell, George E., III
通讯作者：
Howell, George E., III