Potentiation by chronic ethanol treatment of the mitochondrial permeability transition.
Mitochondria isolated from rats chronically fed ethanol were more sensitive to induction of the mitochondrial permeability transition (MPT) by a variety of agents than mitochondria isolated from isocalorically matched controls. The agents utilized have been implicated in both necrotic (Ca(2+)) and apoptotic (ceramide, GD3 ganglioside, and Bax) forms of cell killing and help promote pore opening by differing mechanisms. In each case it was found that concentrations of the inducing agents which promoted little or no pore opening in mitochondria isolated from pair matched controls produced massive MTP opening in mitochondria from chronically ethanol fed rats as evidenced by swelling. In all cases induction of the MPT was prevented by the presence of cyclosporin A.
Pastorino
J G
JG
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107, USA. John Pastorino@mail.tju.edu
Marcineviciute
A
A
Cahill
A
A
Hoek
J B
JB
D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002518:Ceramides / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D005732:Gangliosides / Q000494:pharmacology; D066298:In Vitro Techniques; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009336:Necrosis; D010539:Permeability / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D002518:Ceramides; D005732:Gangliosides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000431:Ethanol; C026226:ganglioside, GD3; D016572:Cyclosporine; D002118:Calcium