L-propionyl-carnitine protection of mitochondria in ischemic rat hearts.
The energy-linked processes (transmembrane potential and oxidative phosphorylation) resulted in impaired mitochondria isolated from ischemic perfused rat hearts. Addition of 1.5 mM L-propionyl-carnitine to the perfusate significantly reduced the ischemic damage and ameliorated mitochondrial Ca2+ homeostasis. In both normoxic and ischemic hearts perfused with L-propionyl-carnitine a consistent amount of propionyl-CoA-otherwise undetectable-was produced. L-propionyl-carnitine treatment also prevented the decrease of succinyl-CoA associated with the ischemic condition. These results and the decrease of myocardial acetyl-CoA induced by exogenous L-propionyl-carnitine points to the anaplerotic effect of this ester. The consequently improved flux in the tricarboxylic-acid cycle may account for the observed protection of mitochondrial functions afforded by L-propionyl-carnitine in the ischemic perfused hearts.
Di Lisa
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F
Centro Studio Fisiologia Mitocondriale, CNR, Università di Padova, Italy.
Menabò
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R
Siliprandi
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N
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003327:Coronary Disease / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000214:Acyl Coenzyme A; C003223:propionylcarnitine; D002331:Carnitine; D002118:Calcium