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Journal Articles Journal of Organometallic Chemistry Year : 2010

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

X. Tekpli
  • Function : Author
M. Rissel
  • Function : Author
Laurence Huc
O. Sergent
  • Function : Author
J. A. Holme
  • Function : Author
M. T. Dimanche-Boitrel
  • Function : Author
D. Lagadic-Gossmann
  • Function : Author


Benzo[a]pyrene (B[a]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[a]P-induced apoptotic process. In this study, we report that B[a]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[a]P exposure. B[a]P also modified fatty acid composition and decreased the cholesterol content of cholesterol-rich microdomains. B[a]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[a]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[a]P-induced membrane remodeling resulted in an intracellular alkalinization observed during the early phase of apoptosis. In conclusion, B[a]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[a]P-induced membrane remodeling was identified as an early apoptotic event leading to an intracellular alkalinization. (C) 2009 Elsevier Inc. All rights reserved.
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Dates and versions

hal-00729575 , version 1 (07-09-2012)


  • HAL Id : hal-00729575 , version 1


X. Tekpli, M. Rissel, Laurence Huc, Daniel D. Catheline, O. Sergent, et al.. Membrane remodeling, an early event in benzo a pyrene-induced apoptosis. Journal of Organometallic Chemistry, 2010, 248, 2 p. ⟨hal-00729575⟩
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