scholarly journals MD2 blockade prevents modified LDL-induced retinal injury in diabetes by suppressing NADPH oxidase-4 interaction with Toll-like receptor-4

2021 ◽  
Author(s):  
Huaicheng Chen ◽  
Tao Yan ◽  
Zongming Song ◽  
Shilong Ying ◽  
Beibei Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Cell Injury ◽  
Critical Role ◽  
Inflammatory Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Modified Ldl ◽  
Nadph Oxidase 4 ◽  
Retinal Injury

AbstractModified LDL-induced inflammation and oxidative stress are involved in the pathogenesis of diabetic retinopathy. Recent studies have also shown that modified LDL activates Toll-like receptor 4 (TLR4) to mediate retinal injury. However, the mechanism by which modified LDL activates TLR4 and the potential role of the TLR4 coreceptor myeloid differentiation protein 2 (MD2) are not known. In this study, we inhibited MD2 with the chalcone derivatives L2H17 and L6H21 and showed that MD2 blockade protected retinal Müller cells against highly oxidized glycated-LDL (HOG-LDL)-induced oxidative stress, inflammation, and apoptosis. MD2 inhibition reduced oxidative stress by suppressing NADPH oxidase-4 (NOX4). Importantly, HOG-LDL activated TLR4 and increased the interaction between NOX4 and TLR4. MD2 was required for the activation of these pathways, as inhibiting MD2 prevented the association of NOX4 with TLR4 and reduced NOX4-mediated reactive oxygen species production and TLR4-mediated inflammatory factor production. Furthermore, treatment of diabetic mice with L2H17 significantly reduced LDL extravasation in the retina and prevented retinal dysfunction and apoptosis by suppressing the TLR4/MD2 pathway. Our findings provide evidence that MD2 plays a critical role in mediating modified LDL-induced cell injury in the retina and suggest that targeting MD2 may be a potential therapeutic strategy.

scholarly journals NADPH oxidase 4 modulates hepatic responses to lipopolysaccharide mediated by Toll-like receptor-4

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Anand Singh ◽  
Bhargav Koduru ◽  
Cameron Carlisle ◽  
Hasina Akhter ◽  
Rui-Ming Liu ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nadph Oxidase 4

Elevated expression of toll-like receptor 4 is associated with NADPH oxidase-induced oxidative stress in B cells of children with autism

2020 ◽  
Vol 84 ◽  
pp. 106555
Author(s):  
Naif O. Al-Harbi ◽  
Ahmed Nadeem ◽  
Sheikh F. Ahmad ◽  
Laila Y. AL-Ayadhi ◽  
Mohammad M. Al-Harbi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
B Cells ◽  
Nadph Oxidase ◽  
Children With Autism ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Elevated Expression

scholarly journals QSYQ Attenuates Oxidative Stress and Apoptosis Induced Heart Remodeling Rats through Different Subtypes of NADPH-Oxidase

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yong Wang ◽  
Chun Li ◽  
Yuli Ouyang ◽  
Tianjiao Shi ◽  
Xiaomin Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Nadph Oxidase ◽  
Caspase 3 ◽  
Ventricular Remodeling ◽  
Cardiac Injury ◽  
Myocardial Tissue ◽  
Therapeutic Effects ◽  
Histological Changes ◽  
Nadph Oxidase 4

We aim to investigate the therapeutic effects of QSYQ, a drug of heart failure (HF) in clinical practice in China, on a rat heart failure (HF) model. 3 groups were divided: HF model group (LAD ligation), QSYQ group (LAD ligation and treated with QSYQ), and sham-operated group. After 4 weeks, rats were sacrificed for cardiac injury measurements. Rats with HF showed obvious histological changes including necrosis and inflammation foci, elevated ventricular remodeling markers levels(matrix metalloproteinases-2, MMP-2), deregulated ejection fraction (EF) value, increased formation of oxidative stress (Malondialdehyde, MDA), and up-regulated levels of apoptotic cells (caspase-3, p53 and tunnel) in myocardial tissue. Treatment of QSYQ improved cardiac remodeling through counter-acting those events. The improvement of QSYQ was accompanied with a restoration of NADPH oxidase 4 (NOX4) and NADPH oxidase 2 (NOX2) pathways in different patterns. Administration of QSYQ could attenuate LAD-induced HF, and AngII-NOX2-ROS-MMPs pathway seemed to be the critical potential targets for QSYQ to reduce the remodeling. Moreover, NOX4 was another key targets to inhibit the p53 and Caspase3, thus to reduce the hypertrophy and apoptosis, and eventually provide a synergetic cardiac protective effect.

scholarly journals Aerobic Training Down-Regulates Pentraxin 3 and Pentraxin 3/Toll-Like Receptor 4 Ratio, Irrespective of Oxidative Stress Response, in Elderly Subjects

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 110
Author(s):  
Brisamar Estébanez ◽  
Alexandra L. Rodriguez ◽  
Nishant P. Visavadiya ◽  
Michael Whitehurst ◽  
María J. Cuevas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aerobic Training ◽  
Oxidative Stress Response ◽  
Pentraxin 3 ◽  
Elderly Adults ◽  
Nitrogen Species ◽  
Toll Like Receptor ◽  
Oxidative Stress Biomarkers ◽  
Toll Like Receptor 4 ◽  
Stress Biomarkers

Reactive oxygen and nitrogen species-mediated cellular aging has been linked to diseases such as atherothrombosis and cancer. Although pentraxin 3 (PTX3) is associated with aging-related diseases via TLR4-dependent anti-inflammatory effects, its relationship with oxidative stress in aging remains to be elucidated. Exercise is proposed as the key intervention for health maintenance in the elderly. This study aimed to examine the association of PTX3 levels with changes in oxidative stress in both plasma and peripheral blood mononuclear cells (PBMCs), following aerobic training in elderly adults. Nine trained and five controls participated in an eight-week aerobic training protocol. Enzyme-linked immunosorbent assay (ELISA) and Western blot analyses were used to determine PTX3, toll-like receptor 4 (TLR4), and levels of oxidative stress biomarkers [3-nitrotyrosine (3NT), 4-hydroxynonenal (4-HNE), glutathione (GSH), protein carbonyl (PC), reactive oxygen/ nitrogen species (ROS/RNS), and trolox equivalent antioxidant capacity (TEAC)] in plasma and/or PBMCs. Results showed a down-regulation of PTX3 expression in PBMCs following aerobic training, along with decreased PTX3/TLR4 ratios. Oxidative stress responses in PBMCs remained unchanged with the exercise protocol. Comparable levels of plasma PTX3 and oxidative stress biomarkers were observed in trained vs. control groups. No correlation was found between PTX3 and any oxidative stress biomarkers following training. These findings demonstrated the down-regulation of PTX3 and PTX3/TLR4 ratio, irrespective of oxidative stress response, in elderly adults following eight weeks of aerobic training.

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