Involvement of Mitochondrial Peroxynitrite in Nitric Oxide-Induced Glutathione Synthesis(Biochemistry/Molecular Biology)
スポンサーリンク
概要
- 論文の詳細を見る
Cells respond to oxidative stress including nitric oxide (NO) by increasing cellular glutathione concentration, as a part of adaptive response against oxidative injury. To elucidate the mechanism by which NO induces glutathione we investigated the reactive oxygen species (ROS) generated in the cell. Treatment of RAW264.7 cells with NO donor, sodium nitroprusside (SNP), resulted in a temporary increase in glutathione in a dose-dependent manner, which peaked between 6h and 12h after treatment, whereas expression of γ-glutamylcysteine synthetase (γ-GCS) mRNA peaked around 3h after treatment. The increase was inhibited by NO scavengers, oxyhemoglobin and carboxyl-2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). N-Acetyl-Lcysteine (NAC) also reduced the increase in glutathione to some extent, whereas both peroxynitrite scavenger ebselen and hydroxyl radical scavenger DMSO inhibited the increase in glutathione in a dose-dependent manner and complete inhibition was observed. Hydrogen peroxide exogenously added to the cell did not increase either glutathione or γ-GCS expression at any concentration, indicating that involvement of hydrogen peroxide is not likely. Flow cytometric analysis showed that SNP induced a marked dose-dependent increase in Rhodamine123 fluorescence, which was completely inhibited by ebselen in a dose-dependent manner, whereas, little increase in 2′, 7′-dichlorofluorescin (DCF) fluorescence was observed. Generation of peroxynitrite in mitochondria by SNP was confirmed by elevated level of nitrotyrosine in a mitochondria fraction isolated from SNP-treated cells, and the elevation was completely inhibited by ebselen as well. These results suggest that induction of glutathione (GSH) synthesis by SNP treatment is mediated by peroxynitrite generated in mitochondria.
- 公益社団法人日本薬学会の論文
- 2005-05-01
著者
-
Kojima Shuji
Faculty Of Pharmaceutical Sciences Science University Of Tokyo
-
Kurozumi Risa
Faculty of Pharmaceutical Sciences, Tokyo University of Science
-
Takahashi Mareyuki
Faculty Of Pharmaceutical Sciences Tokyo University Of Science
-
Kurozumi Risa
Faculty Of Pharmaceutical Sciences Tokyo University Of Science
関連論文
- Effect of Heterocyclic Pyrimidine Compounds on UVB-Induced Cell Damage in Human Keratinocytes and on Melanogenesis in Mouse B16 Cells
- Low-Dose Gamma-Ray Irradiation Induces Translocation of Nrf2 Into Nuclear in Mouse Macrophage RAW264.7 Cells
- Immune Response Pathways in Human Keratinocyte (HaCaT) Cells are Induced by Ultraviolet B via p38 Mitogen-activated Protein Kinase Activation
- A comparative study of nitric oxide, glutathione, and glutathione peroxidase activities in cerebrospinal fluid from children with convulsive diseases/children with aseptic meningitis
- 糖鎖導入ドラッグデリバリー材料開発のためのネオ糖タンパク質・リポソームコンジュゲートの調製と機能評価
- Inhibitory Effects of Prior Low-dose X-ray Irradiation on Carbon Tetrachloride-induced Hepatopathy in Acatalasemic Mice
- Basic Study on the Internal Movement of Inhaled Radon -for Establishment of Experimental Methods -
- The Elevation of p53 Protein Level and SOD Activity in the Resident Blood of the Misasa Radon Hot Spring District
- 22 Biochemical Comparison between Radon Effects and the Other Effects on Humans in Radon Hot Spring Therapy(Low dose and low dose-rate effects, Abstracts of the 46th Annual Meeting of the Japan Radiation Research Society)
- Elevation of Antioxidant Enzymes in the Clinical Effects of Radon and Thermal Therapy for Bronchial Asthma
- Effects of Radon Therapy on Bronchial Asthma
- Mechanisms of Alleviation of Degeneration or Deforming Diseases of Joints by Radon Therapy
- Radon Effects and Thermal Effects on Humans in Radon Therapy
- Immunological effects of The early Radon Therapy at the Misasa Hot Spring
- The Chemical Biological Defense Mechanisms on the Early Radon Therapy at the Misasa Hot Spring
- Suppression of Diabetes by Low Dose γ-Ray Irradiation in Nonobese (NOD) Mice
- Effects of Low Dose Irradiation on Mouse Brain Oxidized by Fe^-NTA
- Inhibitory Effects of Low Dose Irradiation on Fe^ -NTA-induced Hepatopathy in Mice
- Effects of Post Low-dose γ-ray Irradiation on Fatty Liver Induced by Carbon Tetrachloride
- Induction of Glutathione in Mouse Brain by Low Doses of γ-Rays and Its Applicability to Protection and Therapy against Brain Diseases
- Effect of Small Doses of γ-Ray on the Glutathione Level in Mouse Organs.
- Does Small-Dose γ-Ray Radiation Induce Endogenous Antioxidant Potential in Vivo?
- Suppressing Effect of Low-Dose Gamma-Ray Irradiation on Collagen-Induced Arthritis
- ^ Ga-CITRATE ACCUMULATION IN TUMOR CELLS AND HEPARAN SULFATE
- Effect of Repeated Small-Dose γ-Ray Irradiation on Atopic Dermatitis in NC/Nga Mice
- Repeated Irradiations with γ-rays at a Dose of 0.5 Gy May Exacerbate Asthma
- Low-level Nitric Oxide Blunts Oxidant Injury via Up-regulating Glutathione Synthesis
- Involvement of Mitochondrial Peroxynitrite in Nitric Oxide-Induced Glutathione Synthesis(Biochemistry/Molecular Biology)
- Increase of Intracellular Glutathione by Low-Dose γ-Ray Irradiation Is Mediated by Transcription Factor AP-1 in RAW 264.7 Cells(Biochemistry/Molecular Biology)
- Involvement of P2Y receptors in the protective effect of ATP towards the cell damage in HaCaT cells exposed to H_2O_2
- High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging
- Relationship between peroxisome proliferator-activated receptor-γ activation and the ameliorative effects of ascochlorin derivatives on type II diabetes