Comparison of the effects of carnitine palmitoyltransferase-1 and -2 inhibitors on rat heart hypertrophy.
Rats treated orally for 21 days with aminocarnitine, an inhibitor of carnitine palmitoyltransferase-2 (CPT-2), do not show hypertrophy of the heart. This contrasts with the effects of carnitine palmitoyltransferase-1 (CPT-1) inhibitors, that, according to the literature, cause hypertrophy. As CPT-1 and CPT-2 are both required for the oxidation of long-chain fatty acids in mitochondria, it can be concluded that inhibition of fatty acid oxidation per se is not responsible for cell growth, but rather the accumulation of a metabolite, probably long-chain acylcoenzyme A. CPT-1 and CPT-2 inhibitors cause different metabolic changes in the heart. Electron microscopy of hearts fixed 1 hour after Langendorff perfusion with the two types of inhibitors reveals some of these changes. Multilamellar vesicles were observed with aminocarnitine (CPT-2 inhibitor) but not with etomoxir (CPT-1 inhibitor). When both inhibitors were present, electron-dense spots adjacent to mitochondria were observed, possibly containing long-chain acylaminocarnitine.
Hülsmann
W C
WC
Thorax Centre, Rotterdam, The Netherlands.
Peschechera
A
A
Schneijdenberg
C T
CT
Verkleij
A J
AJ
D000818:Animals; D001622:Betaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006332:Cardiomegaly / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D002331:Carnitine; D002333:Carnitine Acyltransferases / Q000037:antagonists & inhibitors; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000187:drug effects; D004852:Epoxy Compounds / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000166:cytology / Q000201:enzymology* / Q000648:ultrastructure; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D004852:Epoxy Compounds; D001622:Betaine; C045761:emeriamine; D002333:Carnitine Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; C054207:etomoxir; D002331:Carnitine