title: Multiple apoptotic pathways induced by p53-dependent acidification in benzo[a]pyrene-exposed hepatic F258 cells.
abstract: Polycyclic aromatic hydrocarbons (PAH), such as benzo[a]pyrene (B[a]P), are ubiquitous genotoxic environmental pollutants. Their DNA-damaging effects lead to apoptosis induction, through similar pathways to those identified after exposure to other DNA-damaging stimuli with activation of p53-related genes and the involvement of the intrinsic apoptotic pathway. However, at a low concentration of B[a]P (50 nM), our previous results pointed to the involvement of intracellular pH (pHi) variations during B[a]P-induced apoptosis in a rat liver epithelial cell line (F258). In the present work, we identified the mitochondrial F0F1-ATPase activity reversal as possibly responsible for pHi decrease. This acidification not only promoted executive caspase activation, but also activated leucocyte elastase inhibitor/leucocyte-derived DNase II (LEI/L-DNase II) pathway. p53 appeared to regulate mitochondria homeostasis, by initiating F0F1-ATPase reversal and endonuclease G (Endo G) release. In conclusion, a low dose of B[a]P induced apoptosis by recruiting a large panel of executioners apparently depending on p53 phosphorylation and, for some of them, on acidification.
authors: Inserm U620, Université Rennes 1, IFR 140, Rennes, France.
authors: Laurence
authors: L
authors: Huc
authors: Mary
authors: M
authors: Rissel
authors: Anita
authors: A
authors: Solhaug
authors: Xavier
authors: X
authors: Tekpli
authors: Morgane
authors: M
authors: Gorria
authors: Alicia
authors: A
authors: Torriglia
authors: Jørn A
authors: JA
authors: Holme
authors: Marie-Thérêse
authors: MT
authors: Dimanche-Boitrel
authors: Dominique
authors: D
authors: Lagadic-Gossmann