title: Bax induces cytochrome c release by multiple mechanisms in mitochondria from MCF7 cells.
abstract: Bax, a pro-apoptotic member of the Bcl-2 family of proteins has the ability to form transmembrane pores large enough to allow cytochrome c (Cyt c) release, as well as to activate the mitochondrial permeability transition pore (mPTP); however, no differential study has been conducted to clarify which one of these mechanisms predominates over the other in the same system. In the present study, we treated isolated mitochondria from MCF7 cells with recombinant protein Bax and tested the efficacy of the mPTP inhibitor cyclosporin A (CsA) and of the Bax channel blocker (Bcb) to inhibit cytochrome c release. We also, induced apoptosis in MCF7 cell cultures with TNF-α plus cycloheximide to determine the effect of such compounds in apoptosis induction via mPTP or Bax oligomerization. Cytochrome c release was totally prevented by CsA and partially by Bcb when apoptosis was induced with recombinant Bax in isolated mitochondria from MCF7 cells. CsA increased the number of living cells in cell culture, as compared with the effect of Bax channel blocker. These results indicate that mPTP activation is the predominant pathway for Bax-induced cytochrome c release from MCF7 mitochondria and for apoptosis induction in the whole cell.
authors.affiliation: Departamento de Fisiología, Biología Celular, Instituto Nacional de Cardiología, "Ignacio Chávez", Juan Badiano No. 1., Col. Sección XVI, México DF, 14080, Mexico.
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Gómez-Crisóstomo
authors.forename: Rebeca
authors.initials: R
authors.lastname: López-Marure
authors.forename: Estrella
authors.initials: E
authors.lastname: Zapata
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zazueta
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez-Abundis
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C494826:BAX protein, human; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D016572:Cyclosporine; D045304:Cytochromes c; D003513:Cycloheximide
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