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

Journal Article · Mon Feb 15 00:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.11.014· OSTI ID:21344867

Tekpli, Xavier; Rissel, Mary; Huc, Laurence ^[1]; Catheline, Daniel ^[2]; Sergent, Odile ^[1]; Rioux, Vincent; Legrand, Philippe ^[2]; Holme, Jorn A ^[3]; Dimanche-Boitrel, Marie-Therese ^[1]; Lagadic-Gossmann, Dominique ^[1]

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1. EA 4427 SeRAIC, Equipe labellisee Ligue contre le Cancer, Universite de Rennes 1, IFR 140, 35043 Rennes cedex (France)
2. Laboratoire de Biochimie, INRA-Agrocampus Rennes, 35042 Rennes (France)
3. Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 404 Torshov, N-4303 Oslo (Norway)

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{sub 2}O{sub 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{sub 2}O{sub 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.

• OSTI ID: 21344867
• Journal Information: Toxicology and Applied Pharmacology, Vol. 243, Issue 1; Other Information: DOI: 10.1016/j.taap.2009.11.014; PII: S0041-008X(09)00480-3; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
BENZOPYRENE
BIOSYNTHESIS
CARCINOGENS
CHOLESTEROL
LIVER
MEMBRANES
MICROSTRUCTURE
POLYCYCLIC AROMATIC HYDROCARBONS
PYRENE
RATS
ANIMALS
AROMATICS
BODY
CONDENSED AROMATICS
DIGESTIVE SYSTEM
GLANDS
HYDROCARBONS
HYDROXY COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANS
RODENTS
STEROIDS
STEROLS
SYNTHESIS
VERTEBRATES