Regulation of cardiac mitochondrial monolysocardiolipin acyltransferase activity and expression during development and in fetal alcohol syndrome.
Fetal alcohol syndrome is a serious developmental disorder and exposure of the fetal heart to alcohol results in disturbances in the biochemistry of all cellular substructures. Mitochondrial effects include diminished respiratory function and physical alteration of the membrane secondary to interaction of ethanol with the hydrophobic region of the bilayer. Cardiolipin is a major mitochondrial membrane phospholipid in the heart and plays an important role in the function of mitochondrial enzymes involved in cellular respiration. We examined the activity of cardiac monolysocardiolipin acyltransferase, a key enzyme responsible for the molecular remodelling of cardiolipin with new fatty acids, in the newborn and adult rat and in new born rats that were exposed to alcohol in utero. Cardiac monolysocardiolipin acyltransferase activities were 57% lower (p < 0.05) in adult rats compared to newborn rats. Cardiac mitochondrial monolysocardiolipin acyltransferase activities were 36% lower (p < 0.05) in newborn rats that were exposed to alcohol in utero and this was due to reduced mitochondrial monolysocardiolipin acyltransferase expression. The results indicate that cardiac mitochondrial monolysocardiolipin acyltransferase activity declines during postnatal development in the rat and that in utero exposure to alcohol inhibits cardiac monolysocardiolipin acyltransferase activity and expression.
Taylor
William A
WA
Department of Pharmacology and Therapeutics, Center for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, Manitoba, Canada.
Legare
Dallas
D
Lautt
W Wayne
WW
Hatch
Grant M
GM
D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000201:enzymology* / Q000235:genetics; D007700:Kinetics; D008929:Mitochondria, Heart / Q000201:enzymology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D005230:Fatty Acids, Nonesterified; D000431:Ethanol; D000217:Acyltransferases; C401969:monolysocardiolipin acyltransferase