c-Jun NH2-terminal kinase-related Na+/H+ exchanger isoform 1 activation controls hexokinase II expression in benzo(a)pyrene-induced apoptosis
| Autor: | Anita Solhaug, Claire Gardyn, Morgane Gorria, Marie-Thérèse Dimanche-Boitrel, Gwenaelle Le Moigne, Dominique Lagadic-Gossmann, Jørn A. Holme, Laurence Huc, Xavier Tekpli, Mary Rissel |
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| Přispěvatelé: | Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), Section for Toxicology, National Veterinary Institute, Division of Environmental Medicine, Institute of Public Health, Institut National de la Santé et de la Recherche Médicale, Ligue Nationale Contre le Cancer (Morbihan, Côte d'Armor, and Ille et Vilaine Comittees), Région Bretagne, Egide (Aurora programme), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
MAP Kinase Kinase 4 Mitochondria Liver chemistry.chemical_compound 0302 clinical medicine Hexokinase MESH: Hexokinase MESH: Animals Phosphorylation MESH: Tumor Suppressor Protein p53 0303 health sciences Sodium-Hydrogen Exchanger 1 biology Kinase apoptosis MESH: Reactive Oxygen Species Liver Oncology Benzo(a)pyrene 030220 oncology & carcinogenesis Mitogen-activated protein kinase MESH: Hydrogen Peroxide MESH: Mitochondria Liver MESH: MAP Kinase Kinase 4 MESH: Cell Nucleus Programmed cell death MESH: Enzyme Activation Sodium-Hydrogen Exchangers MESH: Rats Intracellular pH [SDV.CAN]Life Sciences [q-bio]/Cancer Cell Line 03 medical and health sciences Na+/H+ exchanger 1 MESH: Benzo(a)pyrene polycyclic aromatic hydrocarbon Animals Protein kinase A 030304 developmental biology Cell Nucleus MESH: Sodium-Hydrogen Antiporter MESH: Phosphorylation MESH: Apoptosis JNK Mitogen-Activated Protein Kinases hexokinase II Hydrogen Peroxide MESH: JNK Mitogen-Activated Protein Kinases Molecular biology Rats MESH: Cell Line Enzyme Activation chemistry Apoptosis biology.protein JNK Tumor Suppressor Protein p53 Reactive Oxygen Species MESH: Liver |
| Zdroj: | Cancer Research Cancer Research, 2007, 67 (4), pp.1696-705. ⟨10.1158/0008-5472.CAN-06-2327⟩ Cancer Research, American Association for Cancer Research, 2007, 67 (4), pp.1696-705. ⟨10.1158/0008-5472.CAN-06-2327⟩ |
| ISSN: | 0008-5472 1538-7445 |
| DOI: | 10.1158/0008-5472.CAN-06-2327⟩ |
| Popis: | Regulation of the balance between survival, proliferation, and apoptosis on carcinogenic polycyclic aromatic hydrocarbon (PAH) exposure is still poorly understood and more particularly the role of physiologic variables, including intracellular pH (pHi). Although the involvement of the ubiquitous pHi regulator Na+/H+ exchanger isoform 1 (NHE1) in tumorigenesis is well documented, less is known about its role and regulation during apoptosis. Our previous works have shown the primordial role of NHE1 in carcinogenic PAH-induced apoptosis. This alkalinizing transporter was activated by an early CYP1-dependent H2O2 production, subsequently promoting mitochondrial dysfunction leading to apoptosis. The aim of this study was to further elucidate how NHE1 was activated by benzo(a)pyrene (BaP) and what the downstream events were in the context of apoptosis. Our results indicate that the mitogen-activated protein kinase kinase 4/c-Jun NH2-terminal kinase (MKK4/JNK) pathway was a link between BaP-induced H2O2 production and NHE1 activation. This activation, in combination with BaP-induced phosphorylated p53, promoted mitochondrial superoxide anion production, supporting the existence of a common target for NHE1 and p53. Furthermore, we showed that the mitochondrial expression of glycolytic enzyme hexokinase II (HKII) was decreased following a combined action of NHE1 and p53 pathways, thereby enhancing the BaP-induced apoptosis. Taken together, our findings suggest that, on BaP exposure, MKK4/JNK targets NHE1 with consequences on HKII protein, which might thus be a key protein during carcinogenic PAH apoptosis. [Cancer Res 2007;67(4):1696–705] |
| Databáze: | OpenAIRE |
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