NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation
| Autor: | Andrzej Sienkiewicz, László Forró, Botond Banfi, Olivier Plastre, Lena Serrander, Werner Schlegel, Karl-Heinz Krause, Karen Bedard, Bernard Lardy, Laetitia Cartier |
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| Přispěvatelé: | Facultad de Medicina, GREPI, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Ecole Polytechnique Fédérale de Lausanne (EPFL) |
| Rok vydání: | 2007 |
| Předmět: |
Time Factors
Mitochondrion ddc:616.07 Enzyme Induction/drug effects MESH: Superoxides Biochemistry MESH: Tetracycline Cell Membrane/drug effects/enzymology chemistry.chemical_compound Mice 0302 clinical medicine Cytosol MESH: Cytosol Superoxides Ethidium MESH: Animals Enzyme Inhibitors MESH: NADPH Oxidase chemistry.chemical_classification Enzyme Inhibitors/pharmacology 0303 health sciences NADPH oxidase biology Superoxide MESH: Gene Expression Regulation Enzymologic NOX4 MESH: NAD MESH: Reactive Oxygen Species Mitochondria/drug effects Mitochondria MESH: Nitroblue Tetrazolium MESH: Enzyme Inhibitors NADPH Oxidase 4 Enzyme Induction cardiovascular system MESH: Hydrogen Peroxide NAD/metabolism Superoxides/metabolism MESH: NADP Intracellular Hydrogen Peroxide/pharmacology Research Article MESH: Enzyme Induction RNA Messenger/genetics/metabolism MESH: Mitochondria Gene Expression Regulation Enzymologic/drug effects Gene Expression Regulation Enzymologic Tetracycline/pharmacology Cell Line 03 medical and health sciences Ethidium/analogs & derivatives/pharmacology Animals Humans Cytosol/drug effects/enzymology RNA Messenger [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Molecular Biology MESH: Mice 030304 developmental biology MESH: RNA Messenger Reactive oxygen species MESH: Humans urogenital system NADPH Oxidase/ genetics Nitroblue Tetrazolium MESH: Time Factors Cell Membrane Electron Spin Resonance Spectroscopy NADPH Oxidases Cell Biology Hydrogen Peroxide Tetracycline NADP/metabolism NAD Molecular biology MESH: Ethidium MESH: Cell Line chemistry biology.protein Reactive Oxygen Species/ metabolism MESH: Electron Spin Resonance Spectroscopy NAD+ kinase Reactive Oxygen Species Nitroblue Tetrazolium/pharmacology 030217 neurology & neurosurgery NADP MESH: Cell Membrane |
| Zdroj: | Biochemical Journal Biochemical Journal, Portland Press, 2007, 406 (1), pp.105-14. ⟨10.1042/BJ20061903⟩ Biochemical Journal, Vol. 406, No 1 (2007) pp. 105-114 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/BJ20061903⟩ |
| Popis: | International audience; NOX4 is an enigmatic member of the NOX (NADPH oxidase) family of ROS (reactive oxygen species)-generating NADPH oxidases. NOX4 has a wide tissue distribution, but the physiological function and activation mechanisms are largely unknown, and its pharmacology is poorly understood. We have generated cell lines expressing NOX4 upon tetracycline induction. Tetracycline induced a rapid increase in NOX4 mRNA (1 h) followed closely (2 h) by a release of ROS. Upon tetracycline withdrawal, NOX4 mRNA levels and ROS release decreased rapidly (100 muM). The pattern of NOX4-dependent ROS generation was unique: (i) ROS release upon NOX4 induction was spontaneous without need for a stimulus, and (ii) the type of ROS released from NOX4-expressing cells was H(2)O(2), whereas superoxide (O(2)(-)) was almost undetectable. Probes that allow detection of intracellular O(2)(-) generation yielded differential results: DHE (dihydroethidium) fluorescence and ACP (1-acetoxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine) ESR measurements did not detect any NOX4 signal, whereas a robust signal was observed with NBT. Thus NOX4 probably generates O(2)(-) within an intracellular compartment that is accessible to NBT (Nitro Blue Tetrazolium), but not to DHE or ACP. In conclusion, NOX4 has a distinct pharmacology and pattern of ROS generation. The close correlation between NOX4 mRNA and ROS generation might hint towards a function as an inducible NOX isoform. |
| Databáze: | OpenAIRE |
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