CCL4-INDUCED INCREASE OF HEPATOCYTE FREE ARACHIDONATE LEVEL - PATHOGENESIS AND CONTRIBUTION TO CELL-DEATH

被引:11
作者
CHIARPOTTO, E [1 ]
BIASI, F [1 ]
COMOGLIO, A [1 ]
LEONARDUZZI, G [1 ]
POLI, G [1 ]
DIANZANI, MU [1 ]
机构
[1] UNIV TURIN,DEPT EXPTL MED & ONCOL,GEN PATHOL SECT,CORSO RAFFAELLO 30,I-10125 TURIN,ITALY
关键词
Arachidonic acid; Bioactivation; Carbon tetrachloride; Cell death; Hepatocytes; Phospholipidase A[!sub]2[!/sub;
D O I
10.1016/0009-2797(90)90067-W
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A significant increase of the intracellular level of free arachidonic acid was observed in intact rat hepatocytes after poisoning with very low concentrations of CCl4 (0.129-0.172 mM), shown not to exert direct solvent effect. It seems likely that activation of phospholipase A2 (PLA2) is the mechanism mainly responsible for the rise of cytosolic arachidonate, since the latter is prevented by the PLA2 inhibitors indomethacin and mepacrine. The CCl4-induced delay of arachidonic acid incorporation within the cell membrane phospholipids partly contributes to its intracellular accumulation in the early phases of the poisoning. The lack of any significant protection by metabolic inhibitors (SKF 525A, metyrapone), antioxidant compounds (promethazine, diphenylphenylenediamine DPPD) or antioxidant procedures (rat pretreatment with vitamin E) leads to exclude an involvement of CCl4 biotransformation in the increase of intracellular free arachidonate. Finally, the PLA2 inhibitors employed in this study did not afford protection against the enzymic leakage of CCl4-treated hepatocytes. © 1990.
引用
收藏
页码:195 / 206
页数:12
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