Effect of L-carnitine on the cellular distribution of carnitine and its acyl derivatives in the ischemic heart.
The purpose of this study was to investigate the cellular distribution of carnitine and its acyl derivatives in the normal and ischemic myocardium, and the effects of exogenous 1-carnitine on this distribution and mitochondrial function in the ischemic dog heart. Under non-ischemic conditions, about 93% of the total cellular carnitine was located in the cytosolic compartment and 6.5% in the mitochondrial compartment. Sixty minutes of ischemia induced a decrease in the cytosolic free carnitine content, but caused the accumulation of long-chain acylcarnitine in the cytosolic and mitochondrial compartments. Treatment with 1-carnitine (30 or 100 mg/kg, i.v.) inhibited the mitochondrial accumulation of long-chain acylcarnitine. Free fatty acid (FFA) metabolism in the mitochondria differs from that in the cytosol. So, it is necessary to investigate the changes in FFA metabolism in both of these cellular compartments. Our results suggest that 1-carnitine has a protective effect on the ischemic heart by selectively reducing mitochondrial accumulation of long-chain acylcarnitine.
Fujisawa
S
S
Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
Kobayashi
A
A
Hironaka
Y
Y
Yamazaki
N
N
D000215:Acylation; D000818:Animals; D002331:Carnitine / Q000378:metabolism* / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D002331:Carnitine