Membrane remodeling, an early event in benzo[a]pyrene-induced apoptosis.
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.
Tekpli
Xavier
X
EA 4427 SeRAIC, Equipe labellisée Ligue contre le Cancer, Université de Rennes 1, IFR 140, 35043 Rennes cédex, France.
Rissel
Mary
M
Huc
Laurence
L
Catheline
Daniel
D
Sergent
Odile
O
Rioux
Vincent
V
Legrand
Philippe
P
Holme
Jørn A
JA
Dimanche-Boitrel
Marie-Thérèse
MT
Lagadic-Gossmann
Dominique
D
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
D001564:Benzo(a)pyrene; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid