Acrolein induces apoptosis through the death receptor pathway in A549 lung cells: role of p53.
Acrolein, a highly reactive alpha,beta-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 micromol/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 (approximately 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-alpha 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.
Roy
Julie
J
Département des Sciences Biologiques, TOXEN, Université du Québec à Montréal, CP 8888, Succursale Centre Ville, Montréal, QC H3C 3P8, Canada.
Pallepati
Pragathi
P
Bettaieb
Ahmed
A
Averill-Bates
Diana A
DA
D000171:Acrolein / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D053200:Fas-Associated Death Domain Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D053200:Fas-Associated Death Domain Protein; D017382:Reactive Oxygen Species; D053218:Receptors, Death Domain; D016159:Tumor Suppressor Protein p53; D000171:Acrolein