Multiple apoptotic pathways induced by p53-dependent acidification in benzo[a]pyrene-exposed hepatic F258 cells
✍ Scribed by Laurence Huc; Mary Rissel; Anita Solhaug; Xavier Tekpli; Morgane Gorria; Alicia Torriglia; Jørn A. Holme; Marie-Thérèse Dimanche-Boitrel; Dominique Lagadic-Gossmann
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 531 KB
- Volume
- 208
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
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 (pH~i~) 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 pH~i~ 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. J. Cell. Physiol. 208: 527–537, 2006. © 2006 Wiley‐Liss, Inc.