Gallic Acid Induces Apoptosis of Lung Fibroblasts via a Reactive Oxygen Species-Dependent Ataxia Telangiectasia Mutated-p53 Activation Pathway

2010 ◽  
Vol 58 (5) ◽  
pp. 2943-2951 ◽  
Author(s):  
Cheng-Yen Chuang ◽  
Hsiang-Chun Liu ◽  
Li-Chen Wu ◽  
Chiu-Yuan Chen ◽  
Jinghua Tsai Chang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Gallic Acid ◽  
Ataxia Telangiectasia ◽  
Reactive Oxygen ◽  
Lung Fibroblasts ◽  
Oxygen Species ◽  
Ataxia Telangiectasia Mutated ◽  
Activation Pathway ◽  
P53 Activation

Anti-Oxidant NAC Prevents Hypersensitivity, Immunodeficiency and Lymphomagenesis in Atm−/− Mice.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4753-4753
Author(s):  
Keisuke Ito ◽  
Fumio Arai ◽  
Sahoko Matsuoka ◽  
Yasuo Ikeda ◽  
Toshio Suda ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Ataxia Telangiectasia ◽  
Reactive Oxygen ◽  
Genomic Stability ◽  
Premature Aging ◽  
Antioxidant Systems ◽  
Oxygen Species ◽  
Ataxia Telangiectasia Mutated ◽  
Progressive Cerebellar Ataxia

Abstract Ataxia telangiectasia (A-T) is an autosomal recessive disorder characterized by immunodeficiency, progressive cerebellar ataxia, oculocutaneous telangiectasia, defective spermatogenesis, premature aging and high incidence of lymphoma. A-T is caused by the mutational inactivation of the “ataxia telangiectasia mutated” (ATM) gene. Ataxia telangiectasia mutated (ATM) plays a pivotal role in maintenance of genomic stability. Both A-T patients and Atm−/− mice show humeral and cellular immune defects, including thymic hypoplasia, low number of T-cells and deficiencies of Ig levels. It was originally believed that ATM was not essential for V(D)J recombination in T and B cells, a process which is mediated largely by the nonhomologous end-joining (NHEJ) pathway of DNA repair. However, several studies have revealed that ATM contributes to the prevention of interchromosomal translocations arising from aberrant V(D)J recombination. Thus, it remains unclear how ATM contributes to development of lymphocytes and prevention of lymphoma. It has been shown that deficient ATM function leads to abnormal reactive oxygen species (ROS) control. Several papers reported evidences for increased oxidative stress in tissues from A-T patients or Atm−/− mice, although the mechanism by which ATM regulates ROS level is unclear. Further, abnormalities in the levels and function of antioxidant systems in ATM-deficient cells have been reported. It has been assumed that increased ROS or abnormal response to ROS may contributes to neurodegenerative diseases and premature aging observed in A-T patients. We previously reported a critical role for ATM in stem cell self-renewal due to the effects of this kinase on the regulation of ROS during hematopoiesis. Treatment with the anti-oxidative agent N-acetyl-L-cystine (NAC) prevented the bone marrow failure observed in Atm−/− mice. It was reported that antioxidant prevented tumor development in p53−/− mice. Thus, appropriate ROS control is critical for clinical and cellular phenotypes of tumor-prone disorders. Here we show that a primary cause of immunodeficiency and lymphomagenesis in Atm−/− mice is the elevation of reactive oxygen species (ROS) present in these mutants. Reduction of ROS by NAC prevented the emergence of the senescent phenotype in mouse embryonic fibroblasts and hypersensitivity to total body irradiation in Atm−/− mice. The impairment of immunoglobulin class switch recombination (CSR) seen in Atm−/− mice was also mitigated by NAC, indicating that ROS elevation inhibits physiological DSBs rejoining in vivo. Significantly, in vivo treatment of Atm−/− mice with NAC restored normal T cell development, inhibited aberrant V(D)J recombination, and prevented thymic lymphomagenesis. We conclude that ATM-mediated ROS regulation is essential for the maintenance of genomic stability that prevents immunodeficiency and tumorigenesis. These findings may contribute to effective treatment of A-T patients for prevention of symptoms.

Decreased activation of ataxia telangiectasia mutated (ATM) in monocytes from patients with systemic sclerosis

Rheumatology ◽  
2020 ◽  
Vol 59 (12) ◽  
pp. 3961-3970
Author(s):  
Komei Sakata ◽  
Hidekata Yasuoka ◽  
Keiko Yoshimoto ◽  
Tsutomu Takeuchi
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Ataxia Telangiectasia ◽  
Reactive Oxygen Species Production ◽  
Specific Inhibitor ◽  
Reactive Oxygen ◽  
Healthy Controls ◽  
Oxygen Species ◽  
Ataxia Telangiectasia Mutated ◽  
Species Production

Abstract Objectives The regulation system for oxidative stress in systemic sclerosis (SSc) remains unclear. This study aimed to clarify the possible involvement of ataxia telangiectasia mutated (ATM), which plays a key role in DNA repair and redox balance, in the pathogenesis of SSc. Methods Thirty patients with SSc and 15 healthy controls were enrolled. Expression of ATM and phosphorylated ATM (pATM), an activated form of ATM, in phagocytes in whole blood samples was analysed by FACS. Correlations between expression levels of ATM/pATM and clinical parameters of SSc patients were statistically analysed. Peripheral monocytes were cultured with an ATM-specific inhibitor (KU55933), and reactive oxygen species production in the cells was measured. Results Expression level of pATM in peripheral monocytes and neutrophils from SSc patients was significantly lower than those in healthy controls (P = 0.04 and P < 0.001, respectively), while no significant difference in total ATM expression was observed between SSc and healthy controls. In addition, pATM expression in monocytes of SSc patients with interstitial lung disease or digital pitting scar was remarkably lower than in the patients without these clinical features (P = 0.02 and P = 0.03), respectively. Moreover, pATM expression in monocytes positively correlated with forced vital capacity and negatively correlated with the serum Krebs von den Lungen-6 level. Notably, KU55933, an ATM-specific inhibitor, enhanced reactive oxygen species production by monocytes under oxidative stress. Conclusion Our data revealed that decreased ATM activation in monocytes was associated with SSc-interstitial lung disease and that impaired ATM activation in monocytes may contribute to the disease process of SSc via uncontrolled reactive oxygen species production.

Bergenin Exhibits Hepatoprotective Activity Against Ethanol-Induced Oxidative Stress in ICR Mice

2019 ◽  
Vol 18 (4) ◽  
pp. 297-302
Author(s):  
Sriset Yollada ◽  
Chatuphonprasert Waranya ◽  
Jarukamjorn Kanokwan
Keyword(s):  
Reactive Oxygen Species ◽  
Gallic Acid ◽  
Aspartate Aminotransferase ◽  
Alanine Aminotransferase ◽  
Hepatic Injury ◽  
Reduced Glutathione ◽  
Reactive Oxygen ◽  
Hepatoprotective Activity ◽  
Oxygen Species ◽  
Hepatic Glutathione

Bergenin is a C-glucoside derivative of gallic acid but its antioxidant and hepatoprotective effects have not previously been compared with gallic acid. Male ICR mice were administered bergenin (10, 50, and 250 mg/kg/day) or gallic acid (100 mg/kg/day) for 7 consecutive days before a single administration of ethanol (5 g/kg). Liver sections were histopathologically examined. Aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde levels were determined in plasma. Total glutathione, reduced glutathione, and oxidized glutathione levels were determined in liver homogenates. Ethanol induced hepatic injury with prominent histopathological markers including nuclear pyknosis and necrotic areas and this accorded with increases in the plasma levels of aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde. Moreover, ethanol disturbed hepatic glutathione homeostasis by reducing glutathione stores. Hepatic injury in the ethanol-induced mice was prevented with bergenin and gallic acid by significant decreases in plasma aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde levels and restoration of the hepatic glutathione profile through an increase in the reduced glutathione/oxidized glutathione ratio. Bergenin at 10 mg/kg/day showed comparable hepatoprotective activity to gallic acid in an ethanol-induced mouse model of oxidative stress. Therefore, bergenin might be a promising candidate for further development as a novel hepatoprotective product.

scholarly journals Reactive Oxygen Species Are Required for Maintenance and Differentiation of Primary Lung Fibroblasts in Idiopathic Pulmonary Fibrosis

PLoS ONE ◽  
2010 ◽  
Vol 5 (11) ◽  
pp. e14003 ◽  
Author(s):  
Marialuisa Bocchino ◽  
Savina Agnese ◽  
Evelina Fagone ◽  
Silvia Svegliati ◽  
Domenico Grieco ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Reactive Oxygen ◽  
Lung Fibroblasts ◽  
Oxygen Species

scholarly journals Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells

2010 ◽  
Vol 245 (2) ◽  
pp. 226-235 ◽  
Author(s):  
Young-Ok Son ◽  
J. Andrew Hitron ◽  
Xin Wang ◽  
Qingshan Chang ◽  
Jingju Pan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
P53 Activation

Butein induces cellular senescence through reactive oxygen species‐mediated p53 activation in osteosarcoma U‐2 OS cells

2020 ◽  
Author(s):  
Yung‐Ken Hsu ◽  
Hsuan‐Ying Chen ◽  
Chia‐Chieh Wu ◽  
Ying‐Chih Huang ◽  
Cheng‐Pu Hsieh ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cellular Senescence ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
P53 Activation
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