scholarly journals Novel Curcumin C66 That Protects Diabetes-Induced Aortic Damage Was Associated with Suppressing JNK2 and Upregulating Nrf2 Expression and Function

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Cheng Li ◽  
Xiao Miao ◽  
Shudong Wang ◽  
Binay Kumar Adhikari ◽  
Xin Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Mrna Level ◽  
Protective Mechanisms ◽  
Single Intraperitoneal Injection ◽  
Nrf2 Activation ◽  
Pcr Method ◽  
And Function ◽  
Inflammatory Changes ◽  
Nrf2 Expression

Diabetes-related cardiovascular diseases are leading causes of the mortality worldwide. Our previous study has explored the protective effect of curcumin analogue C66 on diabetes-induced pathogenic changes of the aorta. In the present study, we sought to reveal the underlying protective mechanisms of C66. Diabetes was induced in male WT and JNK2−/− mice with a single intraperitoneal injection of streptozotocin. Diabetic mice and age-matched nondiabetic mice were randomly treated with either vehicle (WT, WT DM, JNK2−/−, and JNK2−/−DM) or C66 (WT + C66, WT DM + C66, JNK2−/− + C66, and JNK2−/−DM + C66) for three months. Aortic oxidative stress, cell apoptosis, inflammatory changes, fibrosis, and Nrf2 expression and function were assessed by immunohistochemical staining for the protein level and real-time PCR method for mRNA level. The results suggested that either C66 treatment or JNK2 deletion can reverse diabetes-induced aortic oxidative stress, cell apoptosis, inflammation, and fibrosis. Nrf2 was also found to be activated either by C66 or JNK2 deletion. However, C66 had no extra effect on diabetic aortic damage or Nrf2 activation without JNK2. These results suggest that diabetes-induced pathological changes in the aorta can be protected by C66 mainly via inhibition of JNK2 and accompanied by the upregulation of Nrf2 expression and function.

scholarly journals Evaluation of antioxidant activation by potential nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Keap1 complex inhibitors

2021 ◽  
Vol 20 (9) ◽  
pp. 1861-1873
Author(s):  
Inas Saleh Almazari ◽  
Shada Youssef Elhayek
Keyword(s):  
Oxidative Stress ◽  
Stress Disorders ◽  
Binding Affinities ◽  
Pathway Activation ◽  
Nrf2 Activation ◽  
Glutamylcysteine Synthetase ◽  
Nrf2 Activator ◽  
Nrf2 Expression ◽  
Activation Capacity ◽  
Mcf 7

Purpose: To investigate the binding affinities of forty-one (41) National Cancer Institute (NCI)-generated compounds, to the Nrf2 ligand, and possible activation of Nrf2 in the MCF-7 cell line.Methods: To investigate the inhibition of the Nrf2/Keap1 complex, the MCF-7 cell line was treated with each of the 41 compounds, at a working concentration of 30 μM. The extent of Nrf2 activation and corresponding Nrf2/Keap1 complex inhibition was evaluated in terms of Nrf2 expression and its antioxidant-associated enzyme gamma-glutamylcysteine synthetase (GCS), using western blotanalysis.Results: Twenty-nine compounds out of the 41 targeted compounds activated GCS, and some showed comparable or greater activation capacity than the standard Nrf2 activator tBHQ. To confirm that the activation of GCS was mediated via Nrf2 activation, cell lysates were tested for their Nrf2 protein expression, and it was found that Nrf2 was activated by the examined compounds for more than 24 h, indicating that the effect of the chosen compounds were not transient.Conclusion: These results might be useful for identifying better targets for cytoprotection, and for oxidative stress alleviation through Nrf2 pathway activation. Further studies are required on the effects of these targets on the prevention and treatment of various oxidative stress disorders, including cancer.

scholarly journals Shikonin Attenuates Acetaminophen-Induced Hepatotoxicity by Upregulation of Nrf2 through Akt/GSK3β Signaling

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 110 ◽  
Author(s):  
Huachao Li ◽  
Yueming Chen ◽  
Jiahao Zhang ◽  
Xiangcui Chen ◽  
Zheng Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Toxicity ◽  
Mrna Level ◽  
Normal Liver ◽  
Close Correlation ◽  
In Vivo Studies ◽  
Gsk 3Β ◽  
Nrf2 Expression ◽  
Apap Hepatotoxicity

Acetaminophen (APAP) overdose-induced acute liver damage is mostly due to overwhelmingly increased oxidative stress. Nuclear factor-erythroid 2-related factor2 (Nrf2) plays an important role in alleviating APAP hepatic toxicity. Shikonin (SHK) enhances Nrf2 in multiple lines of normal cells. Nevertheless, whether SHK protects against APAP-induced liver toxicity remains undefined. This study found SHK defended APAP-induced liver toxicity, as well as reversed the levels of serum alanine/aspartate aminotransferases (ALT/AST), liver myeloperoxidase (MPO) activity, and reactive oxygen species (ROS), while it enhanced the liver glutathione (GSH) level in APAP-treated mice. SHK rescued the cell viability and GSH depletion, but neutralized oxidative stress in APAP-treated human normal liver L-02 cells. Mechanically, SHK increased Nrf2 expression in the exposure of APAP at the protein level but not at the mRNA level. Inhibition of Nrf2 blocked the SHK effect in APAP-treated hepatocytes. Furthermore, SHK improved Nrf2 stability through stimulating PI3K/Akt pathway, thus inhibiting GSK-3β. In vivo studies confirmed the close correlation of liver protection of SHK against APAP and Akt/GSK-3β/Nrf2 pathway. In conclusion, this study reveals that SHK prevents APAP hepatotoxicity by upregulation of Nrf2 via PI3K/Akt/GSK-3β pathway. Therefore, SHK may be a promising candidate against APAP-induced liver injury.

scholarly journals Activation of Nrf2 in Astrocytes Suppressed PD-Like Phenotypes via Antioxidant and Autophagy Pathways in Rat and Drosophila Models

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1850
Author(s):  
Qing Guo ◽  
Bing Wang ◽  
Xiaobo Wang ◽  
Wanli W. Smith ◽  
Yi Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Glial Cells ◽  
Neuroprotective Effect ◽  
Critical Role ◽  
Protective Effects ◽  
Nrf2 Activation ◽  
Autophagy Pathway ◽  
6 Hydroxydopamine ◽  
Nrf2 Expression

The oxidative-stress-induced impairment of autophagy plays a critical role in the pathogenesis of Parkinson’s disease (PD). In this study, we investigated whether the alteration of Nrf2 in astrocytes protected against 6-OHDA (6-hydroxydopamine)- and rotenone-induced PD-like phenotypes, using 6-OHDA-induced rat PD and rotenone-induced Drosophila PD models. In the PD rat model, we found that Nrf2 expression was significantly higher in astrocytes than in neurons. CDDO-Me (CDDO methyl ester, an Nrf2 inducer) administration attenuated PD-like neurodegeneration mainly through Nrf2 activation in astrocytes by activating the antioxidant signaling pathway and enhancing autophagy in the substantia nigra and striatum. In the PD Drosophila model, the overexpression of Nrf2 in glial cells displayed more protective effects than such overexpression in neurons. Increased Nrf2 expression in glial cells significantly reduced oxidative stress and enhanced autophagy in the brain tissue. The administration of the Nrf2 inhibitor ML385 reduced the neuroprotective effect of Nrf2 through the inhibition of the antioxidant signaling pathway and autophagy pathway. The autophagy inhibitor 3-MA partially reduced the neuroprotective effect of Nrf2 through the inhibition of the autophagy pathway, but not the antioxidant signaling pathway. Moreover, Nrf2 knockdown caused neurodegeneration in flies. Treatment with CDDO-Me attenuated the Nrf2-knockdown-induced degeneration in the flies through the activation of the antioxidant signaling pathway and increased autophagy. An autophagy inducer, rapamycin, partially rescued the neurodegeneration in Nrf2-knockdown Drosophila by enhancing autophagy. Our results indicate that the activation of the Nrf2-linked signaling pathways in glial cells plays an important neuroprotective role in PD models. Our findings not only provide a novel insight into the mechanisms of Nrf2–antioxidant–autophagy signaling, but also provide potential targets for PD interventions.

scholarly journals Sulforaphane Attenuation of Type 2 Diabetes-Induced Aortic Damage Was Associated with the Upregulation of Nrf2 Expression and Function

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yonggang Wang ◽  
Zhiguo Zhang ◽  
Wanqing Sun ◽  
Yi Tan ◽  
Yucheng Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Tissue Growth ◽  
Related Factor ◽  
Pathological Changes ◽  
And Function ◽  
Nrf2 Expression

Type 2 diabetes mellitus (T2DM) significantly increases risk for vascular complications. Diabetes-induced aorta pathological changes are predominantly attributed to oxidative stress. Nuclear factor E2-related factor-2 (Nrf2) is a transcription factor orchestrating antioxidant and cytoprotective responses to oxidative stress. Sulforaphane protects against oxidative damage by increasing Nrf2 expression and its downstream target genes. Here we explored the protective effect of sulforaphane on T2DM-induced aortic pathogenic changes in C57BL/6J mice which were fed with high-fat diet for 3 months, followed by a treatment with streptozotocin at 100 mg/kg body weight. Diabetic and nondiabetic mice were randomly divided into groups with and without 4-month sulforaphane treatment. Aorta of T2DM mice exhibited significant increases in the wall thickness and structural derangement, along with significant increases in fibrosis (connective tissue growth factor and transforming growth factor), inflammation (tumor necrosis factor-αand vascular cell adhesion molecule 1), oxidative/nitrative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal), apoptosis, and cell proliferation. However, these pathological changes were significantly attenuated by sulforaphane treatment that was associated with a significant upregulation of Nrf2 expression and function. These results suggest that sulforaphane is able to upregulate aortic Nrf2 expression and function and to protect the aorta from T2DM-induced pathological changes.

Cocoa-rich diet attenuates beta cell mass loss and function in young Zucker diabetic fatty rats by preventing oxidative stress and beta cell apoptosis

2015 ◽  
Vol 59 (4) ◽  
pp. 820-824 ◽  
Author(s):  
Elisa Fernández-Millán ◽  
Isabel Cordero-Herrera ◽  
Sonia Ramos ◽  
Fernando Escrivá ◽  
Carmen Alvarez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beta Cell ◽  
Mass Loss ◽  
Cell Apoptosis ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Apoptosis ◽  
Zucker Diabetic Fatty Rats ◽  
And Function

The Effects of Butyric Acid on the Differentiation, Proliferation, Apoptosis, and Autophagy of IPEC-J2 Cells

2020 ◽  
Vol 20 (4) ◽  
pp. 307-317
Author(s):  
Yuan Yang ◽  
Jin Huang ◽  
Jianzhong Li ◽  
Huansheng Yang ◽  
Yulong Yin
Keyword(s):  
Cell Viability ◽  
P38 Mapk ◽  
Butyric Acid ◽  
Cell Apoptosis ◽  
Mapk Pathway ◽  
Mrna Level ◽  
Dependent Manner ◽  
M Phase ◽  
High Concentrations ◽  
Underlying Mechanisms

Background: Butyric acid (BT), a short-chain fatty acid, is the preferred colonocyte energy source. The effects of BT on the differentiation, proliferation, and apoptosis of small intestinal epithelial cells of piglets and its underlying mechanisms have not been fully elucidated. Methods: In this study, it was found that 0.2-0.4 mM BT promoted the differentiation of procine jejunal epithelial (IPEC-J2) cells. BT at 0.5 mM or higher concentrations significantly impaired cell viability in a dose- and time-dependent manner. In addition, BT at high concentrations inhibited the IPEC-J2 cell proliferation and induced cell cycle arrest in the G2/M phase. Results: Our results demonstrated that BT triggered IPEC-J2 cell apoptosis via the caspase8-caspase3 pathway accompanied by excess reactive oxygen species (ROS) and TNF-α production. BT at high concentrations inhibited cell autophagy associated with increased lysosome formation. It was found that BT-reduced IPEC-J2 cell viability could be attenuated by p38 MAPK inhibitor SB202190. Moreover, SB202190 attenuated BT-increased p38 MAPK target DDIT3 mRNA level and V-ATPase mRNA level that were responsible for normal acidic lysosomes. Conclusion: In conclusion, 1) at 0.2-0.4 mM, BT promotes the differentiation of IPEC-J2 cells; 2) BT at 0.5 mM or higher concentrations induces cell apoptosis via the p38 MAPK pathway; 3) BT inhibits cells autophagy and promotes lysosome formation at high concentrations.

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