Effects of Long-Term Exposure to Copper on the Keap1/Nrf2 Signaling Pathway and Msr-Related Redox Status in the Kidneys of Rats

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.

Download Full-text

Retraction: “MicroRNA‐219 decreases hippocampal long‐term potentiation inhibition and hippocampal neuronal cell apoptosis in type 2 diabetes mellitus mice by suppressing the NMDAR signaling pathway,” by Zhang, L, Chen, Z‐W, Yang, S‐F, et al. CNS Neurosci Ther. 2019; 25: 69–77

CNS Neuroscience & Therapeutics ◽

10.1111/cns.13709 ◽

2021 ◽

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Neuronal Cell ◽

Long Term Potentiation ◽

Term Potentiation

Download Full-text

Melatonin attenuates restenosis after vascular injury in diabetic rats through activation of the Nrf2 signaling pathway

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2021.02.070 ◽

2021 ◽

Vol 548 ◽

pp. 127-133

Author(s):

Xuebin Wang ◽

Tianjia Li ◽

Baitao Ma ◽

Zhewei Zhao ◽

Leng Ni ◽

...

Keyword(s):

Signaling Pathway ◽

Vascular Injury ◽

Diabetic Rats ◽

Nrf2 Signaling Pathway

Download Full-text

Sulforaphane induces colorectal cancer cell proliferation through Nrf2 activation in a p53-dependent manner

Applied Biological Chemistry ◽

10.1186/s13765-020-00578-y ◽

2020 ◽

Vol 63 (1) ◽

Author(s):

Yunjeong Gwon ◽

Jisun Oh ◽

Jong-Sang Kim

Keyword(s):

Colon Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cancer Cell ◽

Related Factor ◽

Mild Stress ◽

Dependent Manner ◽

Cancer Cell Proliferation ◽

Nrf2 Signaling Pathway ◽

Dose Dependent

AbstractSulforaphane is a well-known phytochemical that stimulates nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant cellular response. In this study, we found that sulforaphane promoted cell proliferation in HCT116 human colon cancer cells expressing a normal p53 gene in a dose-dependent but biphasic manner. Since p53 has been reported to contribute to cell survival by regulating various metabolic pathways to adapt to mild stress, we further examined cellular responses in both p53-wild-type (WT) and p53-knockout (KO) HCT116 cells exposed to sulforaphane in vitro and in vivo. Results demonstrated that sulforaphane treatment activated Nrf2-mediated antioxidant enzymes in both p53-WT and p53-KO cells, decreased apoptotic protein expression in WT cells but increased in KO cells in a dose-dependent manner, and increased the expression of a mitochondrial biogenesis marker PGC1α in WT cells but decreased in KO cells. Moreover, a low dose of sulforaphane promoted tumor growth, upregulated the Nrf2 signaling pathway, and decreased apoptotic cell death in p53-WT HCT116 xenografts compared to that in p53-KO HCT116 xenografts in BALB/c nude mice. These findings suggest that sulforaphane can influence colon cancer cell proliferation and mitochondrial function through a crosstalk between the Nrf2 signaling pathway and p53 axis.

Download Full-text

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

Animals ◽

10.3390/ani11082324 ◽

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.

Download Full-text

Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.111552 ◽

2021 ◽

Vol 139 ◽

pp. 111552

Author(s):

Panpan Liu ◽

Jinghan Li ◽

Miaomiao Liu ◽

Muqing Zhang ◽

Yucong Xue ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Ischemia ◽

Signaling Pathway ◽

Nrf2 Signaling Pathway

Download Full-text

Protective Effects of 6,7,4′-Trihydroxyflavanone on Hypoxia-Induced Neurotoxicity by Enhancement of HO-1 through Nrf2 Signaling Pathway

Antioxidants ◽

10.3390/antiox10030341 ◽

2021 ◽

Vol 10 (3) ◽

pp. 341 ◽

Cited By ~ 1

Author(s):

Hyun-Su Lee ◽

Gil-Saeng Jeong

Keyword(s):

Signaling Pathway ◽

Neurodegenerative Disorders ◽

Nuclear Translocation ◽

Protoporphyrin Ix ◽

Protective Role ◽

Osteoclast Formation ◽

Protective Effects ◽

Protein Levels ◽

Nrf2 Signaling Pathway ◽

Pre Treatment

Since hypoxia-induced neurotoxicity is one of the major causes of neurodegenerative disorders, including the Alzheimer’s disease, continuous efforts to find a novel antioxidant from natural products are required for public health. 6,7,4′-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been shown to inhibit osteoclast formation and have an antibacterial activity. However, no evidence has reported whether THF has a protective role against hypoxia-induced neurotoxicity. In this study, we found that THF is not cytotoxic, but pre-treatment with THF has a cytoprotective effect on CoCl2-induced hypoxia by restoring the expression of anti-apoptotic proteins in SH-SY5y cells. In addition, pre-treatment with THF suppressed CoCl2-induced hypoxia-related genes including HIF1α, p53, VEGF, and GLUT1 at the mRNA and protein levels. Pre-treatment with THF also attenuated the oxidative stress occurred by CoCl2-induced hypoxia by preserving antioxidant proteins, including SOD and CAT. We revealed that treatment with THF promotes HO-1 expression through Nrf2 nuclear translocation. An inhibitor assay using tin protoporphyrin IX (SnPP) confirmed that the enhancement of HO-1 by pre-treatment with THF protects SH-SY5y cells from CoCl2-induced neurotoxicity under hypoxic conditions. Our results demonstrate the advantageous effects of THF against hypoxia-induced neurotoxicity through the HO-1/Nrf2 signaling pathway and provide a therapeutic insight for neurodegenerative disorders.

Download Full-text