z-logo
Premium
Activation of caspase‐3‐dependent and ‐independent pathways during 7‐ketocholesterol‐ and 7β‐hydroxycholesterol‐induced cell death: A morphological and biochemical study
Author(s) -
Prunet Céline,
LemaireEwing Stéphanie,
Ménétrier Franck,
Néel Dominique,
Lizard Gérard
Publication year - 2005
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20096
Subject(s) - poly adp ribose polymerase , apoptosis , programmed cell death , dna fragmentation , caspase , propidium iodide , apoptosis inducing factor , cytochrome c , microbiology and biotechnology , caspase 3 , oxysterol , caspase 8 , biology , chemistry , biochemistry , polymerase , enzyme , cholesterol
On treatment with 7‐ketocholesterol (7‐keto) or 7β‐hydroxycholesterol (7β‐OH), which are major oxysterols in atherosclerotic plaques, the simultaneous identification of oncotic and apoptotic cells suggests that these compounds activate different metabolic pathways leading to various modes of cell death. With U937, MCF‐7 (caspase‐3 deficient), MCF‐7/c3 cells (stably transfected with caspase‐3), we demonstrate that caspase‐3 is essential for caspase‐9, ‐7, ‐8 activation, for Bid degradation mediating mitochondrial cytochrome c release, for cleavage of poly(ADP‐ribose) polymerase and inhibitor of the caspase‐activated deoxyribonuclease, and, at least in part, for internucleosomal DNA fragmentation. The crucial role of caspase‐3 was supported by the use of z‐VAD‐fmk and z‐DEVD‐fmk, which abolished apoptosis and the associated events. However, inactivation or lack of caspase‐3 did not inhibit 7‐keto‐ and 7β‐OH‐induced cell death characterized by staining with propidium iodide, loss of mitochondrial potential. The mitochondrial release of apoptosis‐inducing factor and endonuclease G was independent of the caspase‐3 status, which conversely played major roles in the morphological aspects of dead cells. We conclude that caspase‐3 is essential to trigger 7‐keto‐ and 7β‐OH‐induced apoptosis, that these oxysterols simultaneously activate caspase‐3‐dependent and/or ‐independent modes of cell death. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:311–326, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20096

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here