Regulation of the activity of caspases by L-carnitine and palmitoylcarnitine

L-Carnitine facilitates the transport of fatty acids into the mitochondrial matrix where they are used for energy production. Recent studies have show n that L-carnitine is capable of protecting the heart against ischemia/repe rfusion injury and has beneficial effects against Alzheimer's disease and A IDS. The mechanism of action, however, is not yet understood. In the presen t study, me found that in Jurkat cells, L-carnitine inhibited apoptosis ind uced by Fas ligation, In addition, 5 mM carnitine potently inhibited the ac tivity of recombinant caspases 3, 7 and 8, whereas its long-chain fatty aci d derivative palmitoylcarnitine stimulated the activity of all the caspases , Palmitoylcarnitine reversed the inhibition mediated by carnitine. Levels of carnitine and palmitoyl-CoA decreased significantly during. Fas-mediated apoptosis, while palmitoylcarnitine formation increased. These alterations may be due to inactivation of beta-oxidation or to an increase in the acti vity of the enzyme that converts carnitine to palmitoylcarnitine, carnitine palmitoyltransferase I (CPT I). In support of the latter possibility, fibr oblasts deficient in CPT I activity were relatively resistant to staurospor ine-induced apoptosis, These observations suggest that caspase activity may be regulated in part by the balance of carnitine and palmitoylcarnitine. ( C) 2000 Federation of European Biochemical Societies. Published bg Elsevier Science B.V. All rights reserved.