Possible involvement of the adenine nucleotide translocase in the activation of the permeability transition pore induced by cadmium.
Low levels of cadmium induce a rapid calcium efflux in energized rat kidney mitochondria. This is accompanied by the collapse of the transmembrane gradient in a partial CSA-sensitive fashion. The binding of 109Cd2+ to mitochondria is a saturable function; in the presence of NEM, the binding of 2.5 nmol 109Cd2+/mg of protein suffices to induce the opening of the permeability transition pore. It was found that cadmium bound mainly to proteins of molecular weight between 30 and 50 kDa. In the presence of the monothiol reagent NEM, the label is concentrated in the 30 kDa protein. Following the addition of the reducing agent dithiothreitol, calcium is reaccumulated and the membrane potential restored. This correlates with a significant loss of label in the 30 kDa protein region. The 30 kDa protein was identified as the adenine nucleotide translocase by labelling experiments with eosin 5-maleimide and experiments of reconstitution.
Zazueta
C
C
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano No. 1, Colonia Sección XVI, México, D.F. 014080, Mexico. zazueta22@hotmail.com
Sánchez
C
C
García
N
N
Correa
F
F
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004801:Eosine Yellowish-(YS) / Q000031:analogs & derivatives / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D007473:Ion Channels; D007668:Kidney; D008081:Liposomes / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D008970:Molecular Weight; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D013395:Sucrose / Q000378:metabolism
D007473:Ion Channels; D008081:Liposomes; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D002104:Cadmium; D013395:Sucrose; C033531:eosin maleimide; D016572:Cyclosporine; D000226:Mitochondrial ADP, ATP Translocases; D005033:Ethylmaleimide; D002118:Calcium; D004229:Dithiothreitol; D004801:Eosine Yellowish-(YS)