Conversion of CD95 (Fas) Type II into Type I signaling by sub-lethal doses of cycloheximide
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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.
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BRUMATTI, 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.2007.11.003BibTex
@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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