Suppression of T(3)- and fatty acid-induced membrane permeability transition by L-carnitine.
Cytochrome c (Cyt. c) is known to be released from the mitochondria into the cytosol by means of the membrane permeability transition (MPT) mechanism, thereby activating caspase cascade activity, and inducing cell apoptosis. Recently we reported that L-carnitine suppressed palmitoyl-CoA-induced MPT as well as apoptosis in some cell types (Biochem. Pharmacol, in press). In the present study T(3) was found to induce MPT and Cyt. c release, while cyclosporin A (CsA), bovine serum albumin (BSA) and L-carnitine were found to inhibit this action in a concentration-dependent manner. Similarly, long chain fatty acid (LCFA) also induced MPT and Cyt. c release, which was then inhibited by CsA, BSA and L-carnitine. From these results the authors postulate that T(3)-induced MPT is in part regulated by fatty acid metabolism through a dynamic balance between LCFAs and L-carnitine.
Kashiwagi
A
A
Laboratory for Amphibian Biology, Graduate School of Science, Hiroshima University, 739-8526, Higashihiroshima, Japan.
Kanno
T
T
Arita
K
K
Ishisaka
R
R
Utsumi
T
T
Utsumi
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002331:Carnitine / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D005227:Fatty Acids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D010539:Permeability / Q000187:drug effects*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013997:Time Factors; D014284:Triiodothyronine / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D003574:Cytochrome c Group; D005227:Fatty Acids; D014284:Triiodothyronine; D012710:Serum Albumin, Bovine; D016718:Arachidonic Acid; D016572:Cyclosporine; D002331:Carnitine