Cyclophilin A as negative regulator of apoptosis by sequestering cytochrome c.

Abstract

The release of cytochrome c from the mitochondrial intermembrane space is a decisive event in programmed 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.

• Authors: Claude Bonfils, Nicole Bec, Christian Larroque, Maguy Del Rio, Céline Gongora, Martine Pugnière, Pierre Martineau
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 393 Issue 2 Pg. 325-30 (Mar 05 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 20138823 (Publication Type: Journal Article)
• Copyright: 2010 Elsevier Inc. All rights reserved.

Chemical References

• Caspase Inhibitors
• Cytochromes c
• Cyclophilin A

Topics

• Animals
• Apoptosis
• Brain (enzymology)
• Caspase Inhibitors
• Cell Line, Tumor
• Cyclophilin A (metabolism)
• Cytochromes c (metabolism)
• Humans
• Neoplasms (enzymology)
• Neurons (enzymology)