Conversion of CD95 (Fas) Type II into Type I signaling by sub-lethal doses of cycloheximide

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2008
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Brumatti, Gabriela
Yon, Monica
Castro, Fabiola A.
Bueno-da-Silva, Ana Elisa Barreiros
Jacysyn, Jacqueline F.
Amarante-Mendes, Gustavo P.
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Experimental Cell Research. 2008, 314(3), pp. 554-563. ISSN 0014-4827. Available under: doi: 10.1016/j.yexcr.2007.11.003
Zusammenfassung

CD95 (Fas/Apo-1)-mediated apoptosis was shown to occur through two distinct pathways. One involves a direct activation of caspase-3 by large amounts of caspase-8 generated at the DISC (Type I cells). The other is related to the cleavage of Bid by low concentration of caspase-8, leading to the release of cytochrome c from mitochondria and the activation of caspase-3 by the cytochrome c/APAF-1/caspase-9 apoptosome (Type II cells). It is also known that the protein synthesis inhibitor cycloheximide (CHX) sensitizes Type I cells to CD95-mediated apoptosis, but it remains contradictory whether this effect also occurs in Type II cells. Here, we show that sub-lethal doses of CHX render both Type I and Type II cells sensitive to the apoptogenic effect of anti-CD95 antibodies but not to chemotherapeutic drugs. Moreover, Bcl-2-positive Type II cells become strongly sensitive to CD95-mediated apoptosis by the addition of CHX to the cell culture. This is not the result of a restraint of the anti-apoptotic effect of Bcl-2 at the mitochondrial level since CHX-treated Type II cells still retain their resistance to chemotherapeutic drugs. Therefore, CHX treatment is granting the CD95-mediated pathway the ability to bypass the mitochondria requirement to apoptosis, much alike to what is observed in Type I cells.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Apoptosis, Type I, Type II, CD95, Fas, Bid, FLIP, Bcl-2, Cycloheximide
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ISO 690BRUMATTI, Gabriela, Monica YON, Fabiola A. CASTRO, Ana Elisa Barreiros BUENO-DA-SILVA, Jacqueline F. JACYSYN, Thomas BRUNNER, Gustavo P. AMARANTE-MENDES, 2008. Conversion of CD95 (Fas) Type II into Type I signaling by sub-lethal doses of cycloheximide. In: Experimental Cell Research. 2008, 314(3), pp. 554-563. ISSN 0014-4827. Available under: doi: 10.1016/j.yexcr.2007.11.003
BibTex
@article{Brumatti2008-02-01Conve-14270,
  year={2008},
  doi={10.1016/j.yexcr.2007.11.003},
  title={Conversion of CD95 (Fas) Type II into Type I signaling by sub-lethal doses of cycloheximide},
  number={3},
  volume={314},
  issn={0014-4827},
  journal={Experimental Cell Research},
  pages={554--563},
  author={Brumatti, Gabriela and Yon, Monica and Castro, Fabiola A. and Bueno-da-Silva, Ana Elisa Barreiros and Jacysyn, Jacqueline F. and Brunner, Thomas and Amarante-Mendes, Gustavo P.}
}
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