Characterization of a phospholipase A2 in hamster lung and in vitro and in vivo effects of bleomycin on this enzyme.
Phospholipase A2 (PLA2) activity from adult hamster lung was characterized using L-alpha-1-palmitoyl-2-arachidonyl-[arachidonyl-1-14C]-phosphatidylcholine as the substrate. The released [14C]-arachidonic acid was separated by TLC. The enzyme activity increased with increasing incubation time (0-120 minutes), calcium ion concentration (0-25.0 mM) and protein (0-2.0 mg). The optimum pH was 8.0. Deoxycholate had a concentration dependent (0.1 to 0.5 mM) inhibitory effect on the activity. PLA2 specific activity was the highest in mitochondrial fraction. PLA2 activity following incubation with bleomycin was increased in a dose related fashion. In vivo study showed that both PLA2 activity and collagen content in hamster lung were significantly elevated at 14 days followed intratracheal instillation of bleomycin. The activation of PLA2 may play an important role in bleomycin-induced pulmonary toxicity.
Wang
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Department of Veterinary Pharmacology and Toxicology, School of Veterinary Medicine, University of California, Davis 95616.
Giri
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Hyde
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D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001761:Bleomycin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002855:Chromatography, Thin Layer; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D003840:Deoxycholic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D008647:Mesocricetus; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D013997:Time Factors
D001095:Arachidonic Acids; D003840:Deoxycholic Acid; D001761:Bleomycin; D016718:Arachidonic Acid; D003094:Collagen; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium