Membrane fluidity changes are associated with benzo[a]pyrene-induced apoptosis in F258 cells: protection by exogenous cholesterol.
Polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]yrene (B[a]P) constitute a widely distributed class of environmental pollutants, responsible for highly toxic effects. Elucidating the intracellular mechanisms of this cytotoxicity thus remains a major challenge. Besides the activation of the p53 apoptotic pathway, we have previously found in F258 hepatic cells that the B[a]P (50 nM)-induced apoptosis was also dependent upon the transmembrane transporter NHE1, whose activation might result from membrane alterations in our model. We here demonstrate that: (1) B[a]P induces a membrane fluidization surprisingly linked to NHE1 activation; (2) membrane stabilization by exogenous cholesterol protects cells from B[a]P-induced apoptosis, via an effect on late acidification and iron uptake.
Gorria
Morgane
M
INSERM U620, Faculté de Pharmacie, Université de Rennes, and Hôpital Ponchaillou, Rennes cedex, France.
Tekpli
Xavier
X
Sergent
Odile
O
Huc
Laurence
L
Gaboriau
François
F
Rissel
Mary
M
Chevanne
Martine
M
Dimanche-Boitrel
Marie-Thérèse
MT
Lagadic-Gossmann
Dominique
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002460:Cell Line; D008560:Membrane Fluidity; D051381:Rats
D001564:Benzo(a)pyrene