title: Protective action of tamoxifen on carboxyatractyloside-induced mitochondrial permeability transition.
abstract: OBJECTIVE
  Mitochondrial permeability transition is established after massive Ca(2+) accumulation inside the matrix, in addition to an inducer. The closure of the pore can be accomplished by adenosine diphosphate and the immunosuppressant cyclosporin A. Recently, the estrogen antagonist, tamoxifen, has been introduced as an inhibitor of the opening of the permeability transition pore. However, the mechanism by which this drug inhibits pore opening is still under discussion. This work was performed with the purpose of establishing the membrane system involved in tamoxifen-induced pore closure. For this purpose, permeability transition was induced after the addition of carboxyatractyloside, which is a specific reagent that interacts with the adenine nucleotide translocase.
  
  
  METHODS
  Permeability transition was assessed by analyzing matrix Ca(2+) release, transmembrane electric gradient, and mitochondrial swelling in aged, as well as in freshly prepared mitochondria. Also, cytochrome c content was analyzed in membrane mitochondria as well as in the supernatant.
  
  
  RESULTS
  In freshly prepared mitochondria, tamoxifen, at the concentration of 10 μM, totally inhibited nonspecific membrane permeability induced by 1 μM carboxyatractyloside. In addition, tamoxifen inhibited non-specific permeability in aged mitochondria and diminished membrane fluidity.
  
  
  CONCLUSIONS
  Plausibly, the inhibitory effect of tamoxifen on nonspecific membrane permeability, as induced by carboxyatractyloside, should be ascribed to a diminution, of membrane fluidity by this drug.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico DF 014080, Mexico.
authors.forename: Luz
authors.initials: L
authors.lastname: Hernández-Esquivel
authors.lastname: Natalia-Pavón
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zazueta
authors.forename: Noemí
authors.initials: N
authors.lastname: García
authors.forename: Francisco
authors.initials: F
authors.lastname: Correa
authors.forename: Edmundo
authors.initials: E
authors.lastname: Chávez
mesh_terms: D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D051381:Rats; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004965:Estrogen Antagonists; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D013629:Tamoxifen; D001278:Atractyloside; D045304:Cytochromes c; D000226:Mitochondrial ADP, ATP Translocases; C003853:carboxyatractyloside; D002118:Calcium