Identification of disulfide isomerase ERp57 as a target for small molecule cardioprotective agents

RSC Advances ◽  
2015 ◽  
Vol 5 (91) ◽  
pp. 74605-74610 ◽  
Author(s):  
Guozhen Cui ◽  
Luchen Shan ◽  
Ivan Keung Chu ◽  
Guohui Li ◽  
George Pak Heng Leung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Catalytic Activity ◽  
Protective Effect ◽  
Small Molecule ◽  
Inhibitory Effect ◽  
Disulfide Isomerase ◽  
Specific Target ◽  
Proteomic Approach ◽  
Potent Inhibitory Effect

Compound BAA exhibited protective effect against oxidative stress-induced cells injury in H9c2 cardiomyoblast. Chemical proteomic approach identified ERp57 as the specific target for BAA. Furthermore, BAA displayed potent inhibitory effect on the catalytic activity of ERp57.

scholarly journals In Vitro and In Vivo Inhibitory Effect of Citrus Junos Tanaka Peel Extract against Oxidative Stress-Induced Apoptotic Death of Lung Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1231
Author(s):  
Jin Woo Kim ◽  
Eun Hee Jo ◽  
Ji Eun Moon ◽  
Hanvit Cha ◽  
Moon Han Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Inhibitory Effect ◽  
Lung Cells ◽  
In Vivo Models ◽  
Citrus Junos ◽  
Induced Apoptosis ◽  
Peel Extract

Various stresses derived from both internal and external oxidative environments lead to the excessive production of reactive oxygen species (ROS) causing progressive intracellular oxidative damage and ultimately cell death. The objective of this study was to evaluate the protective effects of Citrus junos Tanaka peel extract (CE) against oxidative-stress induced the apoptosis of lung cells and the associated mechanisms of action using in vitro and in vivo models. The protective effect of CE was evaluated in vitro in NCI-H460 human lung cells exposed to pro-oxidant H2O2. The preventive effect of CE (200 mg/kg/day, 10 days) against pulmonary injuries following acrolein inhalation (10 ppm for 12 h) was investigated using an in vivo mouse model. Herein, we demonstrated the inhibitory effect of CE against the oxidative stress-induced apoptosis of lung cells under a highly oxidative environment. The function of CE is linked with its ability to suppress ROS-dependent, p53-mediated apoptotic signaling. Furthermore, we evaluated the protective role of CE against apoptotic pulmonary injuries associated with the inhalation of acrolein, a ubiquitous and highly oxidizing environmental respiratory pollutant, through the attenuation of oxidative stress. The results indicated that CE exhibits a protective effect against the oxidative stress-induced apoptosis of lung cells in both in vitro and in vivo models.

scholarly journals Identification of a novel small molecule that inhibits deacetylase but not defatty-acylase reaction catalysed by SIRT2

2018 ◽  
Vol 373 (1748) ◽  
pp. 20170070 ◽  
Author(s):  
Norio Kudo ◽  
Akihiro Ito ◽  
Mayumi Arata ◽  
Akiko Nakata ◽  
Minoru Yoshida
Keyword(s):  
Small Molecule ◽  
Binding Pocket ◽  
Inhibitory Effect ◽  
Crystallographic Analysis ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Human Pancreatic Cancer ◽  
Chemical Library ◽  
Eukaryotic Translation ◽  
Potent Inhibitory Effect

SIRT2 is a member of the human sirtuin family of proteins and possesses NAD + -dependent lysine deacetylase/deacylase activity. SIRT2 has been implicated in carcinogenesis in various cancers including leukaemia and is considered an attractive target for cancer therapy. Here, we identified NPD11033, a selective small-molecule SIRT2 inhibitor, by a high-throughput screen using the RIKEN NPDepo chemical library. NPD11033 was largely inactive against other sirtuins and zinc-dependent deacetylases. Crystallographic analysis revealed a unique mode of action, in which NPD11033 creates a hydrophobic cavity behind the substrate-binding pocket after a conformational change of the Zn-binding small domain of SIRT2. Furthermore, it forms a hydrogen bond to the active site histidine residue. In addition, NPD11033 inhibited cell growth of human pancreatic cancer PANC-1 cells with a concomitant increase in the acetylation of eukaryotic translation initiation factor 5A, a physiological substrate of SIRT2. Importantly, NPD11033 failed to inhibit defatty-acylase activity of SIRT2, despite its potent inhibitory effect on its deacetylase activity. Thus, NPD11033 will serve as a useful tool for both developing novel anti-cancer agents and elucidating the role of SIRT2 in various cellular biological processes. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.

scholarly journals Cyanidin Attenuates Methylglyoxal-Induced Oxidative Stress and Apoptosis in INS-1 Pancreatic β-Cells by Increasing Glyoxalase-1 Activity

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1319 ◽  
Author(s):  
Tanyawan Suantawee ◽  
Thavaree Thilavech ◽  
Henrique Cheng ◽  
Sirichai Adisakwattana
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Oxidative Dna Damage ◽  
Inhibitory Effect ◽  
Protein Glycation ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glyoxalase 1 ◽  
Its Gene ◽  
Induced Apoptosis

Recently, the mechanisms responsible for anti-glycation activity of cyanidin and its derivatives on the inhibition of methylglyoxal (MG)-induced protein glycation and advanced glycation-end products (AGEs) as well as oxidative DNA damage were reported. In this study, we investigated the protective effect of cyanidin against MG-induced oxidative stress and apoptosis in rat INS-1 pancreatic β-cells. Exposure of cells to cytotoxic levels of MG (500 µM) for 12 h caused a significant reduction in cell viability. However, the pretreatment of cells with cyanidin alone (6.25–100 μM) for 12 h, or cotreatment of cells with cyanidin (3.13–100 μM) and MG, protected against cell cytotoxicity. In the cotreatment condition, cyanidin (33.3 and 100 μM) also decreased MG-induced apoptosis as determined by caspase-3 activity. Furthermore, INS-1 cells treated with MG increased the generation of reactive oxygen species (ROS) during a 6 h exposure. The MG-induced increase in ROS production was inhibited by cyanidin (33.3 and 100 μM) after 3 h stimulation. Furthermore, MG diminished the activity of glyoxalase 1 (Glo-1) and its gene expression as well as the level of total glutathione. In contrast, cyanidin reversed the inhibitory effect of MG on Glo-1 activity and glutathione levels. Interestingly, cyanidin alone was capable of increasing Glo-1 activity and glutathione levels without affecting Glo-1 mRNA expression. These findings suggest that cyanidin exerts a protective effect against MG-induced oxidative stress and apoptosis in pancreatic β-cells by increasing the activity of Glo-1.

Antioxidant Activity and Protective Effect against Oxidative Stress on Hippocampal HT22 Cells of Tea Seed Oil

2018 ◽  
Vol 24 (1) ◽  
pp. 53-59
Author(s):  
Jong Min Kim ◽  
Seon Kyeong Park ◽  
Jin Yong Kang ◽  
Seong-kyeong Bae ◽  
Ga-Hee Jeong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Protective Effect ◽  
Seed Oil ◽  
Ht22 Cells ◽  
Tea Seed Oil

PROTECTIVE EFFECT OF POLYPEPTIDE AND AMINO ACIDS ON THE DEVELOPMENT OF THE NERVOUS TISSUE CULTURE IN THE PRESENCE OF CYCLOPHOSPHAMIDE

2017 ◽  
pp. 22-26
Author(s):  
V. B. Dolgo-Saburov ◽  
N. I. Chalisova ◽  
L. V. Lyanginen ◽  
E. S. Zalomaeva
Keyword(s):  
Amino Acids ◽  
Cell Proliferation ◽  
Tissue Culture ◽  
Protective Effect ◽  
Organotypic Culture ◽  
Inhibitory Effect ◽  
Mustard Gas ◽  
Synthesis Inhibitor ◽  
Combined Administration ◽  
The Central Nervous System

In an organotypic culture, an investigation was conducted into combined effects of cyclophosphamide DNA as synthesis inhibitor used to model a resorptive action of mustard gas, and cortexin polypeptide or each of 20 encoded amino acids on the development of cell proliferation in cerebral cortex explants of the rat. The combined administration of cyclophosphamide together with cortexin or with each of the 20 encoded amino acids, except glycine, showed suppression of the cytostatic agent inhibitory effect. Thus, cortexin and amino acids have a protective effect on cell proliferation in the tissue culture of the central nervous system under the action of mustardlike substances.

Protective effect of DJ-1 against oxidative stress: an advance

2012 ◽  
Vol 32 (1) ◽  
pp. 88-91
Author(s):  
Zhi-yong WANG ◽  
Ling-zhen TANG ◽  
Tian-wen GAO
Keyword(s):  
Oxidative Stress ◽  
Protective Effect

Protective Effect of Swertiamarin on Myocardial Injury Through Activation of Nrf2/HO-1 Pathway in Heart Failure Model of Rats

2020 ◽  
Vol 18 (3) ◽  
pp. 260-265
Author(s):  
Xu Lin ◽  
Zheng Xiaojun ◽  
Lv Heng ◽  
Mo Yipeng ◽  
Tong Hong
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Protective Effect ◽  
Infarct Size ◽  
Rat Model ◽  
Left Ventricular ◽  
Related Factor ◽  
Nuclear Factor ◽  
Internal Dimension

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

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