Acrolein induces apoptosis through the death receptor pathway in A549 lung cells: role of p53This review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease

• Published in: Canadian journal of physiology and pharmacology 2010-03, Vol.88 (3), p.353-368
• Main Authors: Roy, Julie, Pallepati, Pragathi, Bettaieb, Ahmed, Averill-Bates, Diana A
• Format: Article
• Language: English
• Subjects: A549 cell; acrolein; acroléine; apoptose; apoptosis; caspase; cellule A549; death receptor; Fas ligand; ligand Fas; oxidative stress; p53; récepteur de mort; stress oxydatif
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/Y09-134

Acrolein, a highly reactive α, β-unsaturated aldehyde, is an omnipresent environmental pollutant. Chronic and acute human exposures occur through exogenous and endogenous sources, including food, vapors of overheated cooking oil, house and forest fires, cigarette smoke, and automobile exhaust. Acrolein is a toxic byproduct of lipid peroxidation, which has been implicated in pulmonary, cardiac, and neurodegenerative diseases. This study shows that p53 is an initiating factor in acrolein-induced death receptor activation during apoptosis in A549 human lung cells. Exposure of cells to acrolein (0-50 µmol/L) mainly caused apoptosis, which was manifested by execution phase events such as condensation of nuclear chromatin, phosphatidylserine externalization, and poly(ADP-ribose) polymerase (PARP) cleavage. Levels of necrosis (~5%) were low. Acrolein triggered the death receptor pathway of apoptosis, causing elevation of Fas ligand (FasL) and translocation of adaptor protein Fas-associated death domain to the plasma membrane. Acrolein caused activation of caspase-8, caspase-2, caspase-7, and the cross-talk pathway mediated by Bid cleavage. Activation of p53 and increased expression of p53-upregulated modulator of apoptosis (PUMA) occurred in response to acrolein. FasL upregulation and caspase-8 activation were decreased by p53 inhibitor pifithrin- α and antioxidant polyethylene glycol catalase. These findings increase our knowledge about the induction of cell death pathways by acrolein, which has important implications for human health.