Effects of ethanol on phospholipases in the mouse brain, heart and liver.
The activities of microsomal phospholipase A(2) (PLA(2)) and C (PLC) from mouse brain, heart and liver were determined using the substrate 1-palmitoyl-2-N-(4-nitrobenzo-2-oxa-1,3-diazole amino caproyl-phosphatidylcholine (NBD-PC), and the effects of chronic ethanol treatment (ethanol) as well as in vitro addition of various n-alcohols including ethanol on these activities were evaluated. Microsomal membrane fluidity was estimated by diphenylhexatriene anisotropy (gamma). The microsomes from the brain and heart of ethanol-treated mice showed significantly higher PLA(2) activity than those from controls. The brains of ethanol group showed significantly higher PLC activity, while the heart showed significantly lower PLC activity than those of controls. The microsomes from the brain and heart of ethanol-treated mice showed significantly reduced gamma values compared to those of controls. The addition of ethanol in vitro to microsomes was found to increase PLC activity in these tissues, while it decreased PLA(2) activity in a dose-dependent manner. The other n-alcohols showed similar effects on PLA(2) and PLC activity in the live microsomes, while decreases were observed the gamma values in a dose-dependent manner. These results suggest that the change in the membrane fluidity associated with addition of alcohols is a prerequisite for the changes in PLA(2) and PLC activities. In addition, our findings suggest that these changes may play a major role in the cellular injury associated with chronic ethanol treatment in the mouse.
Natsuki
R
R
Faculty of Pharmaceutical Sciences, Setsunan University, Japan.
Yamaguchi
T
T
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000378:metabolism; D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology; D004161:Diphenylhexatriene / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology* / Q000633:toxicity; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008560:Membrane Fluidity / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology; D010713:Phosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*
C078632:1-acyl-2-(12-((7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)dodecanoyl)phosphatidylcholine; D000438:Alcohols; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D010713:Phosphatidylcholines; D004161:Diphenylhexatriene; D000431:Ethanol; D010741:Phospholipases A; D010738:Type C Phospholipases; D009327:4-Chloro-7-nitrobenzofurazan