title: Membrane remodeling, an early event in benzo[a]pyrene-induced apoptosis.
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.
authors.affiliation: EA 4427 SeRAIC, Equipe labellisée Ligue contre le Cancer, Université de Rennes 1, IFR 140, 35043 Rennes cédex, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Tekpli
authors.forename: Mary
authors.initials: M
authors.lastname: Rissel
authors.forename: Laurence
authors.initials: L
authors.lastname: Huc
authors.forename: Daniel
authors.initials: D
authors.lastname: Catheline
authors.forename: Odile
authors.initials: O
authors.lastname: Sergent
authors.forename: Vincent
authors.initials: V
authors.lastname: Rioux
authors.forename: Philippe
authors.initials: P
authors.lastname: Legrand
authors.forename: Jørn A
authors.initials: JA
authors.lastname: Holme
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Dimanche-Boitrel
authors.forename: Dominique
authors.initials: D
authors.lastname: Lagadic-Gossmann
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D021962:Membrane Microdomains / Q000187:drug effects; D008798:Mevalonic Acid; D051381:Rats
chemical_list: D001564:Benzo(a)pyrene; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid