The role of phospholipase A2 in microsomal lipid peroxidation induced with t-butyl hydroperoxide.
The role of phospholipase A2 (PlA2) in lipid peroxidation induced with t-butyl hydroperoxide was examined in rat liver microsomes. Exposure of microsomes to t-butyl hydroperoxide was associated with activation of endogenous PlA2. When PlA2 was inhibited with chlorpromazine, mepacrine, or p-bromphenacyl bromide, the accumulation of thiobarbituric acid reactive substances (TBARS) was reduced in a dose dependent manner. In contrast, the accumulation of conjugated dienes was not affected by chlorpromazine, and was slightly increased by mepacrine. When endogenous PlA2 was activated with mellitin prior to induction of peroxidation, accumulation of both TBARS and dienes was reduced. Analogously, pretreatment with exogenous PlA2 reduced both dienes and TBARS. In contrast, addition of mellitin following the induction of peroxidation did not alter either TBARS or dienes.
Borowitz
S M
SM
Department of Pediatrics, University of Virginia Medical Center, Charlottesville 22908.
Montgomery
C
C
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D015227:Lipid Peroxidation; D008555:Melitten / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D010545:Peroxides / Q000494:pharmacology*; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D013858:Thiobarbiturates; D020122:tert-Butylhydroperoxide
D000098:Acetophenones; D005227:Fatty Acids; D010545:Peroxides; D013858:Thiobarbiturates; D008555:Melitten; D020122:tert-Butylhydroperoxide; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; C029684:thiobarbituric acid; C006821:4-bromophenacyl bromide; D002746:Chlorpromazine