Cyclosporin A Protected Cardiomyocytes Against Oxidative Stress Injury by Inhibition of NF-κB Signaling Pathway

2019 ◽  
Vol 10 (2) ◽  
pp. 329-343 ◽  
Author(s):  
Meng Ma ◽  
Xiaohui Ma ◽  
Jie Cui ◽  
Yifeng Guo ◽  
Xiuqin Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cyclosporin A ◽  
Signaling Pathway ◽  
Stress Injury ◽  
Oxidative Stress Injury

scholarly journals Effect of lentivirus-mediated CFTR overexpression on oxidative stress injury and inflammatory response in the lung tissue of COPD mouse model

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Xiaoli Xu ◽  
Huimin Huang ◽  
Xiangyi Yin ◽  
Hongmei Fang ◽  
Xiaoyue Shen
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Signaling Pathway ◽  
Lung Tissue ◽  
Negative Control ◽  
Chronic Obstructive ◽  
Stress Injury ◽  
Obstructive Pulmonary Disease ◽  
Oxidative Stress Injury

Abstract We aimed to investigate the regulatory mechanism of lentivirus-mediated overexpression of cystic fibrosis transmembrane conductance regulator (CFTR) in oxidative stress injury and inflammatory response in the lung tissue of mouse model of chronic obstructive pulmonary disease (COPD). COPD mouse model induced by cigarette smoke was established and normal mice were used as control. The mice were assigned into a normal group (control), a model group (untreated), an oe-CFTR group (injection of lentivirus overexpressing CFTR), and an oe-NC group (negative control, injection of lentivirus expressing irrelevant sequences). Compared with the oe-NC group, the oe-CFTR group had higher CFTR expression and a better recovery of pulmonary function. CFTR overexpression could inhibit the pulmonary endothelial cell apoptosis, reduce the levels of glutathione (GSH), reactive oxygen species (ROS), and malondialdehyde (MDA) and increase the values of superoxide dismutase (SOD), GSH peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). The overexpression also led to reductions in the white blood cell (WBC) count in alveolus pulmonis, the concentrations of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor-α, and the protein expressions of NF-κB p65, ERK, JNK, p-EPK, and p-JNK related to MAPK/NF-κB p65 signaling pathway. In conclusion, CFTR overexpression can protect lung tissues from injuries caused by oxidative stress and inflammatory response in COPD mouse model. The mechanism behind this may be related to the suppression of MAPK/NF-κB p65 signaling pathway.

scholarly journals Discovery of Therapeutic Candidates for Diabetic Retinopathy Based on Molecular Switch Analysis: Application of a Systematic Process

2022 ◽  
Vol 2022 ◽  
pp. 1-20
Author(s):  
Yue Ren ◽  
Yanan Liu ◽  
Kaiyang Liu ◽  
Xiaoqian Huo ◽  
Chaoqun Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Vascular System ◽  
System Development ◽  
Molecular Switch ◽  
Stress Injury ◽  
Systematic Process ◽  
Oxidative Stress Injury ◽  
Pathogenic Factors ◽  
Nrf2 Signaling Pathway

The pathogenesis of diabetic retinopathy (DR) is complicated, and there is no effective drug. Oxidative stress-induced human retinal microvascular endothelial cells (HRMECs) injury is one of the pathogenic factors for DR. Molecular switches are considered high-risk targets in disease progression. Identification of molecular switch is crucial to interpret the pathogenesis of disease and screen effective ingredients. In this study, a systematic process was executed to discover therapeutic candidates for DR based on HRMECs injury. First of all, the molecular mechanism of HRMECs oxidative stress injury was revealed by transcriptomics and network pharmacology. We found that oxidative stress was one of the pivotal pathogenic factors, which interfered with vascular system development, inflammation, cell adhesion, and cytoskeleton damaged HRMECs through crosstalk. Then, network topology analysis was used to recognize molecular switches. The results indicated that the Keap1-Nrf2-ARE signaling pathway was the molecular switch in HRMECs oxidative stress injury. On this basis, the HEK293-ARE overexpression cell line was applied to obtain 18 active traditional Chinese medicine (TCM) ingredients. Furthermore, andrographolide, one of the 18 candidates, was applied in the HRMECs oxidative stress model to evaluate the accuracy of the systematic process. The efficacy evaluation results showed that andrographolide could regulate oxidative stress, vascular system development, inflammation, adhesion, and skeleton tissue to inhibit HRMECs injury cooperatively. And its mechanism was related to the Nrf2 signaling pathway. Overall, our data suggest that the Nrf2 signaling pathway is the molecular switch in the HRMECs oxidative stress injury. 18 potential Nrf2 agonists are likely to be promising DR candidates.

scholarly journals Overexpression of miR-506-3p Aggravates DBP-Induced Testicular Oxidative Stress in Rats by Downregulating ANXA5 via Nrf2/HO-1 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Min Tang ◽  
Lei Zhang ◽  
Zheng Zhu ◽  
Ran Li ◽  
Shangqian Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Male Rats ◽  
Adolescent Male ◽  
Seminiferous Tubules ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Testicular Injury

Background. Di-N-butylphthalate (DBP) is a kind of unique endocrine toxicity linked to hormonal disruptions that affects the male reproductive system and has given rise to more and more attention. However, the mechanism of DBP-induced testicular injury remains unclear. Here, the objective of this study was to investigate the potential molecular mechanism of miR-506-3p in DBP-induced rat testicular oxidative stress injury via ANXA5 (Annexin A5)/Nrf2/HO-1 signaling pathway. Methods. In vivo, a total of 40 adolescent male rats were treated from 2 weeks with 800 mg/kg/day of DBP in 1 mL/kg corn oil administered daily by oral gavage. Among them, some rats were also injected subcutaneously with 2 nmol agomir-506-3p and/or 10 nmol recombinant rat ANXA5. The pathomorphological changes of testicular tissue were assessed by histological examination, and the antioxidant factors were evaluated. Subsequently, ANXA5, Nrf2, and its dependent antioxidant enzymes, such as HO-1, NQO1, and GST, were detected by Western blotting or immunohistochemical staining. In vitro, TM3 cells (Leydig cells) were used to detect the cell activity by CCK-8 and the transfection in the DBP-treated group. Results. Differentially expressed miRNAs between the DBP-treated and normal rats were analyzed, and qRT-PCR showed miR-506-3p was highly expressed in testicular tissues of the DBP-treated rats. DBP-treated rats presented severe inflammatory infiltration, increased abnormal germ cells, and missed cell layers frequently existed in seminiferous tubules, resulted in oxidative stress and decreased testicular function. Meanwhile, upregulation of miR-506-3p aggravated the above changes. In addition, miR-506-3p directly bound to ANXA5, and overexpression of miR-506-3p could reduce the ANXA5 expression and also decrease the protein levels of Nrf2/HO-1 signaling pathway. Additionally, we found that recombinant rat ANXA5 reversed the DBP-treated testicular oxidative stress promoting injury of miR-506-3p in rats. In vivo results were reproduced in in vitro experiments. Conclusions. This study provided evidence that miR-506-3p could aggravate the DBP-treated testicular oxidative stress injury in vivo and in vitro by inhibiting ANXA5 expression and downregulating Nrf2/HO-1 signaling pathway, which might provide novel understanding in DBP-induced testicular injury therapy.

scholarly journals Protection by genistein on cortical neurons against oxidative stress injury via inhibition of NF-kappaB, JNK and ERK signaling pathway

2015 ◽  
Vol 53 (8) ◽  
pp. 1124-1132 ◽  
Author(s):  
Yisong Qian ◽  
Liangxun Cao ◽  
Teng Guan ◽  
Lan Chen ◽  
Hongbo Xin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Cortical Neurons ◽  
Erk Signaling ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Nf Kappab
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