Modulation by substrates of the protective effect of cyclosporin A on mitochondrial damage.
The influence of substrates on the role of cyclosporin A, to promote the closure of the permeability transition pore, was studied. It was found that in succinate-oxidizing mitochondria, cyclosporin inhibited pore opening as induced by carboxyatractyloside. The opposite occurred when mitochondrial respiration was supported by malate-glutamate, i.e., cyclosporin A was unable to block pore opening promoted by carboxyatractyloside. We propose that the failure of cyclosporin A to induce pore closure could be due to a low NADH matrix content.
Chávez
Edmundo
E
Departamento de Bioquímica, Instituto Nacional de Cardiologia, Ignacio Chávez, México, DF, Mexico. echavez@mail.ssa.gob.mx
Zazueta
Cecilia
C
Correa
Francisco
F
García
Noemí
N
Avilés
César
C
Robles
Sandra G
SG
Rodríguez
César D
CD
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010539:Permeability / Q000187:drug effects; D051381:Rats; D013386:Succinates / Q000378:metabolism
D007166:Immunosuppressive Agents; D013386:Succinates; D009243:NAD; D001278:Atractyloside; D000244:Adenosine Diphosphate; D016572:Cyclosporine; C003853:carboxyatractyloside; D002118:Calcium