Modification of the inhibitory effects of CCl4 on phospholipid and protein biosynthesis by prostacyclin.
CCl4 induced cellular injury and its modification by prostacyclin (PGI2) was studied in cultured rat hepatocytes. Biosynthesis of both intracellular and serum proteins and that of phospholipids decreased upon CCl4 treatments (IC50 7.0, 2.5 and 3.2 mM, respectively). After 1 hr exposure of the cells to CCl4, the reductions in the biosynthesis increased further with time. PGI2 treatments (10(-5)-10(-9) M) of the hepatocytes subsequent to CCl4 poisoning resulted in partial recovery from the cell injury evaluated at the fifth hour of the experiment. Optimal effects of PGI2 were found at a concentration of 10(-7)-10(-8) M, while higher and lower concentrations offered less protection. Upon the addition of CCl4 a higher catabolic rate of PIP2 and an increased formation of inositol phosphates were observed. This alteration was shown to precede the defects in the labelling of the major phospholipid components. Furthermore, these changes were circumvented in the presence of PGI2. Thus, PIP2 metabolism appears to be a critical process in the mechanism of this type of cellular injury and its protection by PGI2.
Divald
A
A
Semmelweis Medical University, Institute of Pathology and Experimental Cancer Research, Budapest, Hungary.
Jeney
A
A
Nagy
J O
JO
Timár
F
F
Lapis
K
K
D000818:Animals; D002251:Carbon Tetrachloride / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D011464:Epoprostenol / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D051381:Rats; D012588:Scintillation Counting
D007295:Inositol Phosphates; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010743:Phospholipids; D002251:Carbon Tetrachloride; D011464:Epoprostenol