Identification of Na+/H+ exchange as a new target for toxic polycyclic aromatic hydrocarbons. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue FASEB Journal Année : 2004

Identification of Na+/H+ exchange as a new target for toxic polycyclic aromatic hydrocarbons.

Laurence Huc
Lydie Sparfel
  • Fonction : Collaborateur
  • PersonId : 857503
Mary Rissel
  • Fonction : Collaborateur
André Guillouzo
  • Fonction : Collaborateur
Olivier Fardel
  • Fonction : Collaborateur

Résumé

The ubiquitous environmental pollutants polycyclic aromatic hydrocarbons are responsible for important carcinogenic and apoptotic effects, whose mechanisms are still poorly understood, owing to the multiplicity of possible cellular targets. Among these mechanisms, alterations of ionic homeostasis have been suggested. In this work, the effects of benzo(a)pyrene [B(a)P] on pHi were tested in the rat liver F258 epithelial cell line, using the fluoroprobe carboxy-SNARF-1. After a 48-h treatment, B(a)P (50 nM) induced an alkalinization, followed by an acidification after 72 h and the development of apoptosis. Determinations of pH(i) recovery following an acid load showed an increased acid efflux at 48 h. Cariporide inhibited both the early alkalinization and the increased acid efflux, thus suggesting the involvement of Na+/H+ exchanger 1 (NHE1). Besides, alpha-naphtoflavone (alpha-NF), an inhibitor of CYP1A1-mediated B(a)P metabolism, prevented all pH(i) changes, and NHE1 activation was blocked by the antioxidant thiourea, which inhibited CYP1A1 metabolism-dependent H2O2 production. Regarding B(a)P-induced apoptosis, this was prevented by alpha-NF and bongkrekic acid, an inhibitor of mitochondria-dependent apoptosis. Interestingly, apoptosis was significantly reduced by cariporide. Taken together, our results indicate that B(a)P, via H2O2 produced by CYP1A1-dependent metabolism, induces an early activation of NHE1, resulting in alkalinization; this appears to play a significant role in mitochondria-dependent B(a)P-induced apoptosis.
Fichier principal
Vignette du fichier
2004Huc-et-alFaseb_1.pdf (1.59 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-02678074 , version 1 (31-05-2020)

Identifiants

Citer

Laurence Huc, Lydie Sparfel, Mary Rissel, Marie-Thérèse Dimanche-Boitre, André Guillouzo, et al.. Identification of Na+/H+ exchange as a new target for toxic polycyclic aromatic hydrocarbons.. FASEB Journal, 2004, 18 (2), pp.344-346. ⟨10.1096/fj.03-0316fje⟩. ⟨hal-02678074⟩
15 Consultations
113 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More