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Bax induces cytochrome c release by multiple mechanisms in mitochondria from MCF7 cells

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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.

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Authors and Affiliations

  1. Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, “Ignacio Chávez”, Juan Badiano No. 1., Col. Sección XVI, México DF, 14080, Mexico

    Cecilia Zazueta & Eduardo Martínez-Abundis

  2. Departamento de Fisiología, Biología Celular, Instituto Nacional de Cardiología, “Ignacio Chávez”, Juan Badiano No. 1., Col. Sección XVI, México DF, 14080, Mexico

    Nancy P. Gómez-Crisóstomo, Rebeca López-Marure & Estrella Zapata

  3. Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad No. 3000, Coyoacán, México DF, 04510, Mexico

    Eduardo Martínez-Abundis

Authors
  1. Nancy P. Gómez-Crisóstomo
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  2. Rebeca López-Marure
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  3. Estrella Zapata
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  4. Cecilia Zazueta
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  5. Eduardo Martínez-Abundis
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Corresponding author

Correspondence to Eduardo Martínez-Abundis.

Additional information

Nancy P. Gómez-Crisóstomo, Rebeca López-Marure and Estrella Zapata are contributed equally to this study.

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Gómez-Crisóstomo, N.P., López-Marure, R., Zapata, E. et al. Bax induces cytochrome c release by multiple mechanisms in mitochondria from MCF7 cells. J Bioenerg Biomembr 45, 441–448 (2013). https://doi.org/10.1007/s10863-013-9508-x

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  • DOI: https://doi.org/10.1007/s10863-013-9508-x

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