Membrane remodeling, an early event in benzo[a]pyrene-induced apoptosis.

X. Tekpli M. Rissel L. Huc Daniel Catheline 1 O. Sergent Vincent Rioux 1 Philippe Legrand 1 J. A. Holme M. T. Dimanche-Boitrel D. Lagadic-Gossmann
1 Laboratoire de Biochimie et Nutrition Humaine
Abstract : Benzo[alpha]pyrene (B[alpha]P) often serves as a model for mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAHs). Our previous work suggested a role of membrane fluidity in B[alpha]P-induced apoptotic process. In this study, we report that B[alpha]P modifies the composition of cholesterol-rich microdomains (lipid rafts) in rat liver F258 epithelial cells. The cellular distribution of the ganglioside-GM1 was markedly changed following B[alpha]P exposure. B[alpha]P also modified fatty acid composition and decreased the cholesterol content of cholesterol-rich microdomains. B[alpha]P-induced depletion of cholesterol in lipid rafts was linked to a reduced expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). Aryl hydrocarbon receptor (AhR) and B[alpha]P-related H(2)O(2) formation were involved in the reduced expression of HMG-CoA reductase and in the remodeling of membrane microdomains. The B[alpha]P-induced membrane remodeling resulted in an intracellular alkalinization observed during the early phase of apoptosis. In conclusion, B[alpha]P altered the composition of plasma membrane microstructures through AhR and H(2)O(2) dependent-regulation of lipid biosynthesis. In F258 cells, the B[alpha]P-induced membrane remodeling was identified as an early apoptotic event leading to an intracellular alkalinization.
Keywords : polyunsaturated fatty-acids stearoyl-CoA desaturase gene-expression hypolipidemic drugs delta-6 desaturase retinoic acid ppar-alpha liver mouse induction
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Journal articles
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Submitted on : Friday, September 7, 2012 - 3:44:50 PM
Last modification on : Monday, August 26, 2019 - 3:53:49 PM

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AGROCAMPUS-OUEST | UNAM | AGROCAMPUS-OUEST-UP-BIOCHIMIE

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X. Tekpli, M. Rissel, L. Huc, Daniel Catheline, O. Sergent, et al.. Membrane remodeling, an early event in benzo[a]pyrene-induced apoptosis.. Toxicology and Applied Pharmacology, Elsevier, 2010, 243 (1), pp.68-76. ⟨10.1016/j.taap.2009.11.014⟩. ⟨hal-00729574⟩

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