Nrf2 signaling pathway in trace metal carcinogenesis: A cross-talk between oxidative stress and angiogenesis

2022 ◽  
pp. 109266
Author(s):  
Mohammad Hassan Emami ◽  
Nasrin Sereshki ◽  
Zahra Malakoutikhah ◽  
Sayed Ali Ehsan Dehkordi ◽  
Alireza Fahim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Trace Metal ◽  
Signaling Pathway ◽  
Cross Talk ◽  
Nrf2 Signaling Pathway ◽  
Metal Carcinogenesis

scholarly journals Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice

2021 ◽  
Vol 22 (11) ◽  
pp. 5995
Author(s):  
Chand Basha Davuljigari ◽  
Frederick Adams Ekuban ◽  
Cai Zong ◽  
Alzahraa A. M. Fergany ◽  
Kota Morikawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Messenger Rna ◽  
Hepatic Necrosis ◽  
Related Factor ◽  
Necrosis Factor Alpha ◽  
Adult Mice ◽  
Nrf2 Signaling Pathway ◽  
Antioxidant Proteins ◽  
Oxide Synthase

Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at 0, 200 or 300 ppm in drinking water and co-administered with subcutaneous injections of sulforaphane, a known activator of the Nrf2 signaling pathway at 0 or 25 mg/kg body weight daily for 4 weeks. Assessments for neurotoxicity, hepatotoxicity, oxidative stress as well as messenger RNA-expression analysis for Nrf2-antioxidant and pro-inflammatory cytokine genes were conducted. Relative to mice exposed only to acrylamide, co-administration of sulforaphane protected against acrylamide-induced neurotoxic effects such as increase in landing foot spread or decrease in density of noradrenergic axons as well as hepatic necrosis and hemorrhage. Moreover, co-administration of sulforaphane enhanced acrylamide-induced mRNA upregulation of Nrf2 and its downstream antioxidant proteins and suppressed acrylamide-induced mRNA upregulation of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in the cerebral cortex. The results demonstrate that activation of the Nrf2 signaling pathway by co-treatment of sulforaphane provides protection against acrylamide-induced neurotoxicity through suppression of oxidative stress and inflammation. Nrf2 remains an important target for the strategic prevention of acrylamide-induced neurotoxicity.

scholarly journals Melatonin Promotes In Vitro Maturation of Vitrified-Warmed Mouse Germinal Vesicle Oocytes, Potentially by Reducing Oxidative Stress through the Nrf2 Pathway

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2324
Author(s):  
Shichao Guo ◽  
Jinyu Yang ◽  
Jianpeng Qin ◽  
Izhar Hyder Qazi ◽  
Bo Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
In Vitro Maturation ◽  
Germinal Vesicle ◽  
Melatonin Receptors ◽  
Development Rates ◽  
Nrf2 Signaling Pathway ◽  
Mouse Gv Oocytes ◽  
Intracellular Oxidative Stress

Previously it was reported that melatonin could mitigate oxidative stress caused by oocyte cryopreservation; however, the underlying molecular mechanisms which cause this remain unclear. The objective was to explore whether melatonin could reduce oxidative stress during in vitro maturation of vitrified-warmed mouse germinal vesicle (GV) oocytes through the Nrf2 signaling pathway or its receptors. During in vitro maturation of vitrified-warmed mouse GV oocytes, there were decreases (p < 0.05) in the development rates of metaphase I (MI) oocytes and metaphase II (MII) and spindle morphology grades; increases (p < 0.05) in the reactive oxygen species (ROS) levels; and decreases (p < 0.05) in expressions of Nrf2 signaling pathway-related genes (Nrf2, SOD1) and proteins (Nrf2, HO-1). However, adding 10−7 mol/L melatonin to both the warming solution and maturation solutions improved (p < 0.05) these indicators. When the Nrf2 protein was specifically inhibited by Brusatol, melatonin did not increase development rates, spindle morphology grades, genes, or protein expressions, nor did it reduce vitrification-induced intracellular oxidative stress in GV oocytes during in vitro maturation. In addition, when melatonin receptors were inhibited by luzindole, the ability of melatonin to scavenge intracellular ROS was decreased, and the expressions of genes (Nrf2, SOD1) and proteins (Nrf2, HO-1) were not restored to control levels. Therefore, we concluded that 10−7 mol/L melatonin acted on the Nrf2 signaling pathway through its receptors to regulate the expression of genes (Nrf2, SOD1) and proteins (Nrf2, HO-1), and mitigate intracellular oxidative stress, thereby enhancing in vitro development of vitrified-warmed mouse GV oocytes.

scholarly journals PO-086 Exercise enhances cardiac antioxidant capacity in diabetic rats through the Keap1/Nrf2 signaling pathway

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Shiqiang Wang
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Diabetic Rats ◽  
Heart Weight ◽  
Stress Injury ◽  
Myocardial Oxidative Stress ◽  
Nrf2 Signaling Pathway ◽  
Gene And Protein Expression

Objective To investigate the effects of exercise on the myocardial oxidative stress injury of diabetic rats, and discussed the role of Keap1/Nrf2 signaling pathway in this process Methods  Tyep 2 diabetic rat model was established by streptozotocin injection through abdominal cavity and high fat diet. The all the diabetic rats were divided into three groups: control group (NC), diabetes group(T2DM) and diabetes exercise group, NC and T2DM group were kept quiet for 8 weeks, T2DME group was trained for 8 weeks. After the exercise, weight, heart weight and blood were measured. MDA, T-SOD and GSH-PX enzyme were measured by biochemical method. Ho-1, Keap1, Nrf2 gene and protein expression were detected by RT-PCR and WesternBlotting. Results Compared with NC group, the weight of rats in the T2DM group significantly decreased [(528+/-71g vs 362+/-33g), P<0.05], HWI  significantly increased [(2.845+/-0.22 vs 3.841+/-0.21, P <0.05], blood glucose was significantly increased [(6.4±3.8 vs 26±7.5mmol/L), P <0.01],T-SOD and GSH-PX activity decreased significantly (P<0.05), Ho-1 protein expression increased (P<0.01), Keap1 and Nrf2 showed no significant changes, and Nrf2 nuclear transposition decreased (P<0.05). Compared with the T2DM group, no significant change in body weight and heart weight in the T2DME group, with significant decrease in HWI[（3.841±0.21 vs 3.235±0.23），P＜0.05], with significant decrease in blood glucose [（26.0±7.5 vs 21.0±6.8），P＜0.05]. Ho-1 gene and protein expression increased significantly（P＜0.05and P＜0.01）, with no significant change of Keap1, while Nrf2 expression increased significantly (P < 0.05), and Nrf2 nuclear transposition increased significantly (P < 0.01). Conclusions Exercise activates the myocardial Keap1/Nrf2 signaling pathway in rats, promotes the expression of downstream antioxidant enzymes, increases cardiac antioxidant capacity, and resists diabetic myocardial oxidative stress injury.

scholarly journals Ganoderic Acid D Protects Human Amniotic Mesenchymal Stem Cells against Oxidative Stress-Induced Senescence through the PERK/NRF2 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Yan Xu ◽  
Huan Yuan ◽  
Yi Luo ◽  
Yu-Jie Zhao ◽  
Jian-Hui Xiao
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Signaling Pathway ◽  
Adult Stem Cells ◽  
Telomerase Activity ◽  
Related Factor ◽  
Dependent Manner ◽  
Ganoderic Acid ◽  
Nrf2 Signaling Pathway

Aging is an important risk factor in the occurrence of many chronic diseases. Senescence and exhaustion of adult stem cells are considered as a hallmark of aging in organisms. In this study, a senescent human amniotic mesenchymal stem cell (hAMSC) model subjected to oxidative stress was established in vitro using hydrogen peroxide. We investigated the effects of ganoderic acid D (GA-D), a natural triterpenoid compound produced from Ganoderma lucidum, on hAMSC senescence. GA-D significantly inhibited β-galactosidase (a senescence-associated marker) formation, in a dose-dependent manner, with doses ranging from 0.1 μM to 10 μM, without inducing cytotoxic side-effects. Furthermore, GA-D markedly inhibited the generation of reactive oxygen species (ROS) and the expression of p21 and p16 proteins, relieved the cell cycle arrest, and enhanced telomerase activity in senescent hAMSCs. Furthermore, GA-D upregulated the expression of phosphorylated protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK), peroxidase III (PRDX3), and nuclear factor-erythroid 2-related factor (NRF2) and promoted intranuclear transfer of NRF2 in senescent cells. The PERK inhibitor GSK2656157 and/or the NRF2 inhibitor ML385 suppressed the PERK/NRF2 signaling, which was activated by GA-D. They induced a rebound for the generation of ROS and β-galactosidase-positive cells and attenuated the differentiation capacity. These findings suggest that GA-D retards hAMSC senescence through activation of the PERK/NRF2 signaling pathway and may be a promising candidate for the discovery of antiaging agents.

Sign in / Sign up

Export Citation Format

Share Document