On the opening of an insensitive cyclosporin A non-specific pore by phenylarsine plus mersalyl.
The purpose of this work was addressed to provide new information on the effect of thiol reagents on mitochondrial non-specific pore opening, and its response to cyclosporin A (CSA). To meet this proposal phenylarsine oxide (PHA) and mersalyl were employed as tools to induce permeability transition and CSA to inhibit it. PHA-induced mitochondrial dysfunction, characterized by Ca2+ efflux, swelling, and membrane de-energization, was inhibited by N-ethylmaleimide and CSA. Conversely, mersalyl failed to inhibit the inducing effect of phenylarsine oxide, it rather strengthened it. In addition, the effect of mersalyl was associated with cross-linking of membrane proteins. The content of membrane thiol groups accessible to react with PHA, mersalyl, and PHA plus mersalyl was determined. In all situations, permeability transition was accompanied by a significant decrease in the whole free membrane thiol content. Interestingly, it is also shown that mersalyl hinders the protective effect of cyclosporin A on PHA-induced matrix Ca2+ efflux.
García
Noemí
N
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano # 1, Col. Sección XVI, Tlalpam, Mexico, DF, 014080, Mexico. ngarciar@salud.gob.mx
Martínez-Abundis
Eduardo
E
Pavón
Natalia
N
Chávez
Edmundo
E
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents; D016572:Cyclosporine / Q000494:pharmacology*; D005033:Ethylmaleimide / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008634:Mersalyl / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D018272:Porins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013439:Sulfhydryl Reagents / Q000737:chemistry / Q000494:pharmacology
D001152:Arsenicals; D003432:Cross-Linking Reagents; D018272:Porins; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; C029341:oxophenylarsine; D008634:Mersalyl; D016572:Cyclosporine; D000226:Mitochondrial ADP, ATP Translocases; D005033:Ethylmaleimide; D002118:Calcium