Different mechanisms involved in apoptosis following exposure to benzo[a]pyrene in F258 and Hepa1c1c7 cells
| Autor: | Olivier Fardel, Dominique Lagadic-Gossmann, Volker M. Arlt, Nina E. Landvik, Xavier Tekpli, Jørn A. Holme, Laurence Huc, Anita Solhaug, Morgane Gorria, Steinar Øvrebø |
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| Přispěvatelé: | Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Section for Toxicology, National Veterinary Institute, Division of Environmental Medicine, Institute of Public Health, Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UR), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Holme, Jørn A |
| Rok vydání: | 2006 |
| Předmět: |
Cell signaling
MESH: Hydrogen-Ion Concentration Cell MESH: Aryl Hydrocarbon Hydroxylases Apoptosis Mitochondrion Toxicology Membrane Potentials Mice 0302 clinical medicine MESH: Animals Extracellular Signal-Regulated MAP Kinases MESH: Extracellular Signal-Regulated MAP Kinases bcl-2-Associated X Protein 0303 health sciences Cytochrome c MESH: Reactive Oxygen Species General Medicine Hydrogen-Ion Concentration 3. Good health Cell biology Mitochondria Benzo[a]pyrene MESH: Cytochrome P-450 CYP1A1 medicine.anatomical_structure MESH: Cell Survival Liver Proto-Oncogene Proteins c-bcl-2 MESH: Epithelial Cells 030220 oncology & carcinogenesis Cytochrome P-450 CYP1B1 Aryl Hydrocarbon Hydroxylases MESH: Rats MESH: Mitochondria Cell Survival Intracellular pH Biology Cell Line 03 medical and health sciences Bcl-2-associated X protein MESH: Benzo(a)pyrene medicine Benzo(a)pyrene Cytochrome P-450 CYP1A1 MESH: Membrane Potentials Animals MESH: bcl-2-Associated X Protein [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Mice 030304 developmental biology MESH: Proto-Oncogene Proteins c-akt MESH: Apoptosis DNA adducts Epithelial Cells MESH: Cell Line Rats Metabolism MESH: Proto-Oncogene Proteins c-bcl-2 Cell culture biology.protein Reactive Oxygen Species Proto-Oncogene Proteins c-akt MESH: Liver |
| Zdroj: | Chemico-Biological Interactions Chemico-Biological Interactions, Elsevier, 2007, 167 (1), pp.41-55. ⟨10.1016/j.cbi.2007.01.008⟩ Chemico-Biological Interactions, 2007, 167 (1), pp.41-55. ⟨10.1016/j.cbi.2007.01.008⟩ Chemico Biological Interactions 1 (167), 41-55. (2007) |
| ISSN: | 0009-2797 |
| DOI: | 10.1016/j.cbi.2007.01.008⟩ |
| Popis: | The present study compares and elucidates possible mechanisms why B[a]P induces different cell signals and triggers apparently different apoptotic pathways in two rather similar cell lines (hepatic epithelial cells of rodents). The rate and maximal capacity of metabolic activation, as measured by the formation of B[a]P-tetrols and B[a]P-DNA adducts, was much higher in mouse hepatoma Hepa1c1c7 cells than in rat liver epithelial F258 cells due to a higher induced level of cyp1a1. B[a]P increased intracellular pH in both cell lines, but this change modulated the apoptotic process only in F258 cells. In Hepa1c1c7 cells reactive oxygen species (ROS) production appeared to be a consequence of toxicity, unlike F258 cells in which it was an initial event. The increased mitochondrial membrane potential found in F258 cells was not observed in Hepa1c1c7 cells. Surprisingly, F258 cells cultured at low cell density were somewhat more sensitive to low (50nM) B[a]P concentrations than Hepa1c1c7 cells. This could be explained partly by metabolic differences at low B[a]P concentrations. In contrast to the Hepa1c1c7 model, no activation of cell survival signals including p-Akt, p-ERK1/2 and no clear inactivation of pro-apoptotic Bad was observed in the F258 model following exposure to B[a]P. Another important difference between the two cell lines was related to the role of Bax and cytochrome c. In Hepa1c1c7 cells, B[a]P exposure resulted in a "classical" translocation of Bax to the mitochondria and release of cytochrome c, whereas in F258 cells no intracellular translocation of these two proteins was seen. These results suggest that the rate of metabolism of B[a]P and type of reactive metabolites formed influence the resulting balance of pro-apoptotic and anti-apoptotic cell signaling, and hence the mechanisms involved in cell death and the chances of more permanent genetic damage. The study has been supported by an Aurora grant (Egide) and Cancer Research, UK and the financial support is greatly appreciated. Volker M. Arlt is a member of the Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS) EU Network of Excellence. We thank Ingrid V. Botnen and Leni Ekeren for skilled technical assistance. We wish to thank the microscopy platform and Dr. Dutertre (UMR 6061, CNRS, Rennes) for helpful advice on immunolocalization captures and analyzes. |
| Databáze: | OpenAIRE |
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