title: Ebselen induces mitochondrial permeability transition because of its interaction with adenine nucleotide translocase.
abstract: OBJECTIVE
  Mitochondrial permeability transition is a process established through massive Ca(2+) load in addition to an inducer reagent. Ebselen (Ebs), an antioxidant seleno compound, has been introduced as a reagent which inhibits mitochondrial dysfunction induced by permeability transition. Paradoxically enough, it has been shown that Ebs may also be able to induce the opening of the mitochondrial non-selective pores. This study was performed with the purpose of establishing the membrane system involved in Ebs-induced pore opening.
  
  
  METHODS
  Permeability transition was appraised by analyzing the following: i) matrix Ca(2+) release, and mitochondrial swelling, ii) efflux of cytochrome c, and iii) the inhibition of superoxide dismutase. All of these adverse reactions were inhibited by N-ethylmaleimide and cyclosporin A.
  
  
  RESULTS
  At concentrations from 5 to 20 μM, we found that Ebs induces non-specific membrane permeability. Remarkably, Ebs blocks the binding of the fluorescent reagent eosin-5-maleimide to the thiol groups of the adenine nucleotide translocase.
  
  
  CONCLUSIONS
  Based on the above, it is tempting to hypothesize that Ebs induces pore opening through its binding to the ADP/ATP carrier.
authors: Departamento de Farmacología, Instituto Nacional de Cardiología, Ignacio Chávez, México D. F. 014080, México.
authors: Natalia
authors: N
authors: Pavón
authors: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico.
authors: Francisco
authors: F
authors: Correa
authors: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico.
authors: Mabel
authors: M
authors: Buelna-Chontal
authors: Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico.
authors: Luz
authors: L
authors: Hernández-Esquivel
authors: Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico. Electronic address: echavez@salud.gob.mx.
authors: Edmundo
authors: E
authors: Chávez
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001278:Atractyloside; D001393:Azoles / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D054833:Isoindoles; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects*; D051381:Rats
chemical_list: D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D001278:Atractyloside; C042986:ebselen; D000226:Mitochondrial ADP, ATP Translocases; D002118:Calcium
keywords: ADP/ATP translocase; Calcium; Ebselen; Mitochondria; Permeability transition