Expression and characterization of recombinant bifunctional enzymes with glutathione peroxidase and superoxide dismutase activities

Guan, Tuchen; Song, Jian; Wang, Yanan; Guo, Liying; Yuan, Lin; Zhao, Yue; Gao, Yuan; Lin, Liangru; Wang, Yali; Wei, Jingyan

doi:10.1016/j.freeradbiomed.2017.06.005

Cited by 21 publications

(16 citation statements)

References 35 publications

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“…Then, we proved that activation of Nrf2 by CPUY192018 significantly enhanced the antioxidant capacity of HK-2 cells on behalf of the enhancing activity of key antioxidant enzymes including SOD, CAT and GPx and the upregulation of the GSH/GSSG ratio. SOD gives protection by directly scavenging superoxide radicals and hydrogen peroxide (H 2 O 2 ), converting them to less reactive species [52]. SOD catalyses the dismutation of the superoxide radical (•O 2 ) to H 2 O 2 , which is one of the major enzymes that protect cells from ROS [53].…”

Section: Discussionmentioning

confidence: 99%

CPUY192018, a potent inhibitor of the Keap1-Nrf2 protein-protein interaction, alleviates renal inflammation in mice by restricting oxidative stress and NF-κB activation

et al. 2019

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The Keap1-Nrf2-ARE pathway regulates the constitutive and inducible transcription of various genes that encode detoxification enzymes, antioxidant proteins and anti-inflammatory proteins and has pivotal roles in the defence against cellular oxidative stress. In this study, we investigated the therapeutic potential of CPUY192018 , a potent small-molecule inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI), in renal inflammation. In human proximal tubular epithelial HK-2 cells, CPUY192018 treatment significantly increased Nrf2 protein level and Nrf2 nuclear translocation, which enhanced Nrf2-ARE transcription capacity and the downstream protein content in a Nrf2 dependent manner. In lipopolysaccharide (LPS)-challenged human HK-2 cells, CPUY192018 exhibited cytoprotective effects by enhancing the Nrf2-ARE regulated antioxidant system and diminished the LPS-induced inflammatory response by hindering the ROS-mediated activation of the NF-κB pathway. In the LPS-induced mouse model of chronic renal inflammation, by activating Nrf2, CPUY192018 treatment balanced renal oxidative stress and suppressed inflammatory responses. Hence, administration of CPUY192018 reduced kidney damage and ameliorated pathological alterations of the glomerulus. Taken together, our study suggested that small-molecule Keap1-Nrf2 PPI inhibitors can activate the Nrf2-based cytoprotective system and protect the kidney from inflammatory injury, raising a potential application of Keap1-Nrf2 PPI inhibitors in the treatment of inflammatory kidney disorders.

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Section: Discussionmentioning

confidence: 99%

CPUY192018, a potent inhibitor of the Keap1-Nrf2 protein-protein interaction, alleviates renal inflammation in mice by restricting oxidative stress and NF-κB activation

et al. 2019

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“…Non-enzymatic antioxidants are mainly vitamins E, vitamin C, glutathione, nitric oxide, β-carotene, etc. Enzyme antioxidants include superoxide dismutase, catalase and glutathione peroxidase [28,29]. Superoxide dismutase plays the first role in scavenging reactive oxygen species (ROS).…”

Section: Discussionmentioning

confidence: 99%

Response of Wumeng Semi-Fine Wool Sheep to Copper-Contaminated Environment

Wu¹,

Shen²

2020

Pol. J. Environ. Stud.

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We evaluated the response of Wumeng semi-fine wool sheep to a copper-contaminated environment and found an action plan to solve copper pollution through a grazing experiment and ammonium molybdate supplementary experiment carried out in Weining County of Guizhou Province in China. The content of heavy metal element in soil, herbage, and animal tissues was measured by atomic absorption spectrometry, and the blood physiological and biochemical indicators were determined by animalspecific automatic blood analyzer and automatic biochemical analyzer respectively. The results showed that the copper content in soil and herbage of contaminated pasture was significantly higher than that in control pasture, and the copper content in blood and liver in affected sheep was significantly higher than that in the control group. Hemoglobin (Hb), red blood cell count (RBC), hematocrit (PCV), mean corpuscular volume (MCV) contents and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in affected sheep were significantly lower than those in control, while the activities of ceruloplasmin (CP), glutamic oxaloacetic transaminase (GOT), creatine phosphokinase (CPK) and malondialdehyde (MDA) were significantly higher. There was no significant difference in the level of mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and white blood cell count (WBC) between the affected and control sheep. After supplementation of ammonium molybdate, copper content in blood and liver decreased gradually, and the abnormal blood indexes recovered. At the end of the ammonium molybdate supplementation experiment, Wumeng semi-fine wool sheep in the drug-control group (CK group) showed hemoglobinuria, jaundice, anemia and other symptoms. Conclusion: a copper-contaminated environment seriously affected mineral metabolism and blood physiological and biochemical indicators of Wumeng semi-fine wool sheep, and we can utilize the antagonism of molybdenum and copper in the diet to achieve the goal of harmless utilization of a copper-polluted meadow.

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“…Activation of lipid peroxidation (LPO) is one of the trigger mechanisms of stress damage with disorder of the cellular metabolism, which is first of all associated with damage of cellular and subcellular membranes [5][6][7][8]. There are systems of antioxidant protection to neutralize excess of LPO and maintain a steady intracellular concentration of free radicals and lipoperoxide in the body [9,10]. Flavonoid corvitin has an antioxidant, antiischemic, membrane-stabilizing, and immunomodulating effect [11,12].…”

Section: Introductionmentioning

confidence: 99%

Effects of quercetin on antioxidant potential in the experimental periodontitis development

Demkovych

Bondarenko

Hasiuk

2019

Interventional Medicine and Applied Science

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The results of experimental research of antioxidant system are presented in this article. Superoxide dismutase activity, catalase, and ceruloplasmin have been determined on the 7th and 14th days of experimental periodontitis development both without correction and with the injection of a water-soluble quercetin drug (corvitin). Hence, there was a decrease in superoxide dismutase activity, intensive increase in catalase activity, and ceruloplasmin maintenance in the blood serum during acute period of inflammatory process. The usage of flavonoid for 7 days resulted in stabilization of radical oxidation due to reduction of superoxide dismutase activity, maintenance at the high-level catalase activity, and ceruloplasmin concentration in the rat’s blood plasma with experimental bacterial-immune periodontitis.

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Expression and characterization of recombinant bifunctional enzymes with glutathione peroxidase and superoxide dismutase activities

Cited by 21 publications

References 35 publications

CPUY192018, a potent inhibitor of the Keap1-Nrf2 protein-protein interaction, alleviates renal inflammation in mice by restricting oxidative stress and NF-κB activation

CPUY192018, a potent inhibitor of the Keap1-Nrf2 protein-protein interaction, alleviates renal inflammation in mice by restricting oxidative stress and NF-κB activation

Response of Wumeng Semi-Fine Wool Sheep to Copper-Contaminated Environment

Effects of quercetin on antioxidant potential in the experimental periodontitis development

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