Cyclophilin A as negative regulator of apoptosis by sequestering cytochrome c |
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Authors: | Claude Bonfils Nicole Bec Maguy Del Rio Martine Pugnière |
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Institution: | a IRCM, INSERM U896, UM1, CRLC Val d’Aurelle-Paul Lamarque, Montpellier, France b CNRS, UMR5236, UM1-UM2, Faculté de Pharmacie, Montpellier, France |
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Abstract: | The release of cytochrome c from the mitochondrial intermembrane space is a decisive event in programed cell death. Once in the cytoplasm, cytochrome c is involved in the formation of the macromolecular complex termed apoptosome, which activates procaspase-9 which in turn activates downstream procaspase-3. There are increasing evidence indicating that cyclophilin A is highly expressed in many tumors and cell lines where it exerts an anti-apoptotic function. In brain tissue, which over-expresses constitutively cyclophilin A, we found mixed dimers composed of cyclophilin A and cytochrome c. In a cell-free system we observed that pure cyclophilin A inhibited cytochrome c-dependent procaspase-3 activation. Moreover, we detected cyclophilin A-cytochrome c complexes within the cytoplasm of HCT116 cells following staurosporine-induced apoptosis. Our results strongly support that, in tumor cells, cyclophilin A is able to inhibit procaspase-3 activation by sequestering cytochrome c. |
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Keywords: | Apoptosis Brain Tumor Cyclophilin A Cytochrome c Procaspase-3 Phosphatidylethanolamine-binding protein |
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