The aldehyde acrolein induces apoptosis via activation of the mitochondrial pathway.
Acrolein is a highly reactive alpha,beta-unsaturated aldehyde, which is a product of lipid peroxidation. It is an environmental pollutant that has been implicated in multiple respiratory diseases. Acrolein is produced by the enzymatic oxidative deamination of spermine by amine oxidase. Oxidation products of polyamines have been involved in the inhibition of cell proliferation, apoptosis, and the inhibition of DNA and protein synthesis. The present study investigates the mechanism of cell death induced by acrolein. Acrolein induced apoptosis through a decrease in mitochondrial membrane potential, the liberation of cytochrome c, the activation of initiator caspase-9, and the activation of the effector caspase-7. However, acrolein inhibited enzymatic activity of the effector caspase-3, although a cleavage of pro-caspase-3 occurred. The activation of caspases-9 and -7 was confirmed by the cleavage of their pro-enzyme form by acrolein. Apoptosis was inhibited by an inhibitor of caspase-9, but not by an inhibitor of caspase-3. The induction of apoptosis by acrolein was confirmed morphologically by the condensation of nuclear chromatin and by the cleavage of the inhibitor of caspase activated DNase (ICAD), which leads to the liberation of CAD that causes DNA fragmentation. These results demonstrate that acrolein causes apoptosis through the mitochondrial pathway.
Tanel
André
A
Département de chimie et de biochimie, TOXEN, Université du Québec à Montréal CP 8888, Succursale Centre Ville, Montréal, Québec, Canada H3C 3P8.
Averill-Bates
Diana A
DA
D000171:Acrolein / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D053453:Caspase 9; D061945:Caspase Inhibitors; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D007425:Intracellular Membranes / Q000187:drug effects; D008564:Membrane Potentials; D008928:Mitochondria / Q000187:drug effects*; D009336:Necrosis; D013997:Time Factors
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D000171:Acrolein; D053453:Caspase 9