Nicotine mediates oxidative stress and apoptosis through cross talk between NOX1 and Bcl-2 in lung epithelial cells

Zanetti, Filippo; Giacomello, Marta; Donati, Yves Richard; Carnesecchi, Stéphanie; Frieden, Maud; Barazzone, Constance

doi:10.1016/j.freeradbiomed.2014.08.002

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Title		Nicotine mediates oxidative stress and apoptosis through cross talk between NOX1 and Bcl-2 in lung epithelial cells
Authors		Zanetti, Filippo Giacomello, Marta Donati, Yves Richard Carnesecchi, Stéphanie Frieden, Maud Barazzone, Constance
Published in		Free radical biology & medicine. 2014, vol. 76, p. 173-84
Abstract		Nicotine contributes to the onset and progression of several pulmonary diseases. Among the various pathophysiological mechanisms triggered by nicotine, oxidative stress and cell death are reported in several cell types. We found that chronic exposure to nicotine (48h) induced NOX1-dependent oxidative stress and apoptosis in primary pulmonary cells. In murine (MLE-12) and human (BEAS-2B) lung epithelial cell lines, nicotine acted as a sensitizer to cell death and synergistically enhanced apoptosis when cells were concomitantly exposed to hyperoxia. The precise signaling pathway was investigated in MLE-12 cells in which NOX1 was abrogated by a specific inhibitor or stably silenced by shRNA. In the early phase of exposure (1h), nicotine mediated intracellular Ca(2+) fluxes and activation of protein kinase C, which in its turn activated NOX1, leading to cellular and mitochondrial oxidative stress. The latter triggered the intrinsic apoptotic machinery by modulating the expression of Bcl-2 and Bax. Overexpression of Bcl-2 completely prevented nicotine's detrimental effects, suggesting Bcl-2as a downstream key regulator in nicotine/NOX1-induced cell damage. These results suggest that NOX1 is a major contributor to the generation of intracellular oxidative stress induced by nicotine and might be an important molecule to target in nicotine-related lung pathologies.
Identifiers		DOI: 10.1016/j.freeradbiomed.2014.08.002 PMID: 25151121
Full text		Article (Published version) (5.8 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique
Research group		Facteurs influençants le développement pulmonaire: étude translationnelle chez l'animal et l'homme (182)
Citation (ISO format)		ZANETTI, Filippo et al. Nicotine mediates oxidative stress and apoptosis through cross talk between NOX1 and Bcl-2 in lung epithelial cells. In: Free radical biology & medicine, 2014, vol. 76, p. 173-84. doi: 10.1016/j.freeradbiomed.2014.08.002 https://archive-ouverte.unige.ch/unige:48447