AMPK/p38/Nrf2 activation as a protective feedback to restrain oxidative stress and inflammation in microglia stimulated with sodium fluoride

AbstractCurcumin, a phytochemical extracted from Curcuma longa rhizomes, is known to be protective in neurons via activation of Nrf2, a master regulator of endogenous defense against oxidative stress in cells. However, the exact mechanism by which curcumin activates Nrf2 remains controversial. Here, we observed that curcumin induced the expression of genes downstream of Nrf2 such as HO-1, NQO1, and GST-mu1 in neuronal cells, and increased the level of Nrf2 protein. Notably, the level of p62 phosphorylation at S351 (S349 in human) was significantly increased in cells treated with curcumin. Additionally, curcumin-induced Nrf2 activation was abrogated in p62 knockout (−/−) MEFs, indicating that p62 phosphorylation at S351 played a crucial role in curcumin-induced Nrf2 activation. Among the kinases involved in p62 phosphorylation at S351, PKCδ was activated in curcumin-treated cells. The phosphorylation of p62 at S351 was enhanced by transfection of PKCδ expression plasmid; in contrast, it was inhibited in cells treated with PKCδ-specific siRNA. Together, these results suggest that PKCδ is mainly involved in curcumin-induced p62 phosphorylation and Nrf2 activation. Accordingly, we demonstrate for the first time that curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at S351.

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Effects of sodium fluoride and Ocimum sanctum extract on the lifespan and climbing ability of Drosophila melanogaster

The Journal of Basic and Applied Zoology ◽

10.1186/s41936-021-00229-8 ◽

2021 ◽

Vol 82 (1) ◽

Author(s):

Sidra Perveen ◽

Shalu Kumari ◽

Himali Raj ◽

Shahla Yasmin

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Drosophila Melanogaster ◽

Sodium Fluoride ◽

Ocimum Sanctum ◽

Activity Assay ◽

Lipid Peroxidation Assay ◽

Climbing Ability ◽

The Impact ◽

Sublethal Concentrations

Abstract Background Fluoride may induce oxidative stress and apoptosis. It may also lead to neurobehavioural defects including neuromuscular damage. The present study aimed to explore the effects of sub lethal concentrations of sodium fluoride (NaF) on the lifespan and climbing ability of Drosophila melanogaster. In total, 0.6 mg/L and 0.8 mg/L of NaF were selected as sublethal concentrations of NaF for the study. Lifespan was measured and climbing activity assay was performed. Results The study showed significant decrease in lifespan of flies treated with fluoride. With increasing age, significant reduction in climbing activity was observed in flies treated with sodium fluoride as compared to normal (control) flies. Flies treated with tulsi (Ocimum sanctum) and NaF showed increase in lifespan and climbing activity as compared to those treated with NaF only. Lipid peroxidation assay showed significant increase in malondialdehyde (MDA) values in the flies treated with NaF as compared to control. The MDA values decreased significantly in flies treated with tulsi mixed with NaF. Conclusions The results indicate that exposure to sub lethal concentration of NaF may cause oxidative stress and affect the lifespan and climbing activity of D. melanogaster. Tulsi extract may help in reducing the impact of oxidative stress and toxicity caused by NaF.

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Keap1 deletion accelerates mutant K-ras/p53-driven cholangiocarcinoma

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00296.2019 ◽

2020 ◽

Vol 318 (3) ◽

pp. G419-G427 ◽

Cited By ~ 3

Author(s):

Tatsuhide Nabeshima ◽

Shin Hamada ◽

Keiko Taguchi ◽

Yu Tanaka ◽

Ryotaro Matsumoto ◽

...

Keyword(s):

Oxidative Stress ◽

Cancer Progression ◽

Stress Responses ◽

Target Genes ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Related Factor ◽

Loss Of Function ◽

P53 Expression ◽

Nrf2 Activation

The activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) pathway contributes to cancer progression in addition to oxidative stress responses. Loss-of-function Keap1 mutations were reported to activate Nrf2, leading to cancer progression. We examined the effects of Keap1 deletion in a cholangiocarcinoma mouse model using a mutant K-ras/ p53 mouse. Introduction of the Keap1 deletion into liver-specific mutant K-ras/ p53 expression resulted in the formation of invasive cholangiocarcinoma. Comprehensive analyses of the gene expression profiles identified broad upregulation of Nrf2-target genes such as Nqo1 and Gstm1 in the Keap1-deleted mutant K-ras/ p53 expressing livers, accompanied by upregulation of cholangiocyte-related genes. Among these genes, the transcriptional factor Sox9 was highly expressed in the dysplastic bile duct. The Keap-Nrf2-Sox9 axis might serve as a novel therapeutic target for cholangiocarcinoma. NEW & NOTEWORTHY The Keap1-Nrf2 system has a wide variety of effects in addition to the oxidative stress response in cancer cells. Addition of the liver-specific Keap1 deletion to mice harboring mutant K-ras and p53 accelerated cholangiocarcinoma formation, together with the hallmarks of Nrf2 activation. This process involved the expansion of Sox9-positive cells, indicating increased differentiation toward the cholangiocyte phenotype.

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In Vivo Protective Effects of Gallic Acid Isolated from Peltiphyllum Peltatum Against Sodium Fluoride-Induced Oxidative Stress in Rat Erythrocytes

Archives of Industrial Hygiene and Toxicology ◽

10.2478/10004-1254-64-2013-2353 ◽

2013 ◽

Vol 64 (4) ◽

pp. 553-559 ◽

Cited By ~ 12

Author(s):

Seyed Fazel Nabavi ◽

Solomon Habtemariam ◽

Antoni Sureda ◽

Akbar Hajizadeh Moghaddam ◽

Maria Daglia ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Superoxide Dismutase ◽

Vitamin C ◽

Gallic Acid ◽

Sodium Fluoride ◽

Enzyme Activities ◽

Control Group ◽

Rat Erythrocytes ◽

Pre Treatment

Abstract Gallic acid has been identified as an antioxidant component of the edible and medicinal plant Peltiphyllum peltatum. The present study examined its potential protective role against sodium fluoride (NaF)-induced oxidative stress in rat erythrocytes. Oxidative stress was induced by NaF administration through drinking water (1030.675 mg m-3 for one week). Gallic acid at 10 mg kg-1 and 20 mg kg-1 and vitamin C for positive controls (10 mg kg-1) were administered daily intraperitoneally for one week prior to NaF administration. Thiobarbituric acid reactive substances, antioxidant enzyme activities (superoxide dismutase and catalase), and the level of reduced glutathione were evaluated in rat erythrocytes. Lipid peroxidation in NaF-exposed rats significantly increased (by 88.8 %) when compared to the control group (p<0.05). Pre-treatment with gallic acid suppressed lipid peroxidation in erythrocytes in a dose-dependent manner. Catalase and superoxide dismutase enzyme activities and glutathione levels were reduced by NaF intoxication by 54.4 %, 63.69 %, and 42 % (p<0.001; vs. untreated control group), respectively. Pre-treatment with gallic acid or vitamin C significantly attenuated the deleterious effects. Gallic acid isolated from Peltiphyllum peltatum and vitamin C mitigated the NaF-induced oxidative stress in rat erythrocytes.

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