Expression of monolysocardiolipin acyltransferase activity is regulated in concert with the level of cardiolipin and cardiolipin biosynthesis in the mammalian heart.
BACKGROUND
Monolysocardiolipin acyltransferase (MLCL AT) catalyzes the acylation of monolysocardiolipin to cardiolipin in mammalian tissues. We previously reported that cardiac cardiolipin levels, MLCL AT and cardiolipin synthase activities were all elevated in rats made hyperthyroid by thyroxine treatment. In this study, we examined if cardiac mitochondrial MLCL AT activity was dependent upon the biosynthesis and level of cardiolipin in the heart. Rat heart mitochondrial MLCL AT activity was determined under conditions in which the levels of cardiac cardiolipin and cardiolipin synthase activity were either reduced or unaltered using four different disease models in the rat. In addition, these parameters were examined in a murine model of cardiac cell differentiation.


RESULTS
In rats made hypothyroid by treatment with 6-n-propyl-2-thiouracil in the drinking water for 34 days, cardiac cardiolipin content was decreased 29% (p < 0.025) and this was associated with a 32% decrease (p < 0.025) in cardiolipin synthase and a 35% reduction (p < 0.025) in MLCL AT activities. Streptozotocin-induced diabetes or hyperinsulinemia in rats did not affect cardiac cardiolipin content nor MLCL AT and cardiolipin synthase activities. Finally, cardiolipin content, MLCL AT and cardiolipin synthase activities were unaltered during murine P19 teratocarcinoma cell differentiation into cardiac myocytes. In all models, phospholipase A2 activities were unaltered compared with controls.


CONCLUSIONS
We propose a general model in which the expression of MLCL AT activity is regulated in concert with the biosynthesis and level of cardiolipin in the heart.
Taylor
William A
WA
Department of Pharmacology, Centre on Aging, University of Manitoba, Winnipeg, Canada. taylorw@ms.umanitoba.ca
Xu
Fred Y
FY
Ma
Brian J
BJ
Mutter
Thomas C
TC
Dolinsky
Vernon W
VW
Hatch
Grant M
GM
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006946:Hyperinsulinism / Q000201:enzymology / Q000378:metabolism; D007037:Hypothyroidism / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017855:Transferases (Other Substituted Phosphate Groups) / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002308:Cardiolipins; D008565:Membrane Proteins; D012333:RNA, Messenger; D000217:Acyltransferases; C401969:monolysocardiolipin acyltransferase; D017855:Transferases (Other Substituted Phosphate Groups); C100091:cardiolipin synthetase