Skip to Main content Skip to Navigation
Journal articles

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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [46 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00130324
Contributor : Alicia Torriglia <>
Submitted on : Sunday, February 11, 2007 - 4:37:17 PM
Last modification on : Tuesday, August 11, 2020 - 9:14:02 PM
Long-term archiving on: : Friday, November 25, 2016 - 3:02:14 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Citation

Laurence Huc, Mary Rissel, Anita Solhaug, Xavier Tekpli, Morgane Gorria, et al.. Multiple apoptotic pathways induced by p53-dependent acidification in benzo[a]pyrene-exposed hepatic F258 cells.. Journal of Cellular Physiology, Wiley, 2006, 208 (3), pp.527-37. ⟨10.1002/jcp.20686⟩. ⟨inserm-00130324⟩

Share

Metrics

Record views

331