Involvement of Nrf2 and mitochondrial apoptotic signaling in trehalose protection against cadmium-induced kidney injury

Metallomics ◽  
2020 ◽  
Author(s):  
Rui-Feng Fan ◽  
Zi-Fa Li ◽  
Dong Zhang ◽  
Zhen-Yong Wang
Keyword(s):  
Protective Effect ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Apoptotic Signaling ◽  
Nrf2 Signaling Pathway

Trehalose exerted its renal protective effect via inhibiting cadmium-activated Nrf2 signaling pathway, which was closely related with mitochondrial apoptotic signaling pathway.

scholarly journals Protective Effect of Tempol on Acute Kidney Injury Through PI3K/Akt/Nrf2 Signaling Pathway

2016 ◽  
Vol 41 (2) ◽  
pp. 129-138 ◽  
Author(s):  
Gensheng Zhang ◽  
Qiaoling Wang ◽  
Qin Zhou ◽  
Renjun Wang ◽  
Minze Xu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Nrf2 Signaling Pathway

scholarly journals The Protective Effect of Static Magnetic Fields with Different Magnetic Inductions against Fluoride Toxicity Is Related to the NRF2 Signaling Pathway

2020 ◽  
Vol 10 (18) ◽  
pp. 6509
Author(s):  
Magdalena Kimsa-Dudek ◽  
Agata Krawczyk ◽  
Agnieszka Synowiec-Wojtarowicz
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Magnetic Induction ◽  
Redox Homeostasis ◽  
Fluoride Toxicity ◽  
Static Magnetic Fields ◽  
Nrf2 Signaling Pathway

A redox imbalance disrupts the cellcycle and the proliferation process, and contributes to the initiation of programmed cell death. One of the pathways that are important for redox homeostasis is the Nrf2-ARE signaling pathway. Fluoride as well as static magnetic fields (SMF) are associated with the concepts of oxidative stress, and thus programmed cell death. Therefore, this study aimed to assess the connection between oxidative stress and apoptosis in human cells co-exposed to fluoride and a SMF with a different magnetic induction and to determine whether the Nrf2-signaling pathway is involved in these effects. The research was realized using normal human dermal fibroblasts that had been co-exposed to fluoride (0.3 mmol/L) and a SMF with a different magnetic induction (0.45 T, 0.55 T, 0.65 T) for 12 h. The mRNA levels of the cellular antioxidant system-related genes and apoptosis-related genes were assessed using the quantitative reverse transcription polymerase chain reaction (RT-qPCR) method. Our results indicated that the increased activity of antioxidant enzymes (SOD1 (superoxide dismutase 1), SOD2 and GSR (glutathione reductase)) suggests the restoration of the cell redox homeostasis that had been disturbed by fluoride, and also that the genes whose expression is associated with the induction of apoptosis are down regulated as a result of exposure to a SMF. The SMF with a 0.65 T flux density had the strongest effect on the fibroblasts. Moreover, our findings demonstrated that the Nrf2 transcription factor plays a crucial role in the protective effect of a SMF against fluoride toxicity in human cells. The results of these studies can form the basis for developing therapeutic strategies for apoptosis and oxidative stress-related diseases.

scholarly journals Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the Akt/GSK-3β/Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 5/6 Nephrectomized Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Hong-feng Zhang ◽  
Jia-hong Wang ◽  
Yan-li Wang ◽  
Cheng Gao ◽  
Yan-ting Gu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Dependent Manner ◽  
Salvianolic Acid ◽  
Nrf2 Signaling Pathway ◽  
Antioxidative Effects ◽  
Dose Dependent

Salvianolic acid A (SAA) is a bioactive polyphenol extracted from Salviae miltiorrhizae Bunge, which possesses a variety of pharmacological activities. In our previous study, we have demonstrated that SAA effectively attenuates kidney injury and inflammation in an established animal model of 5/6 nephrectomized (5/6Nx) rats. However, there has been limited research regarding the antioxidative effects of SAA on chronic kidney disease (CKD). Here, we examined the antioxidative effects and underlying mechanisms of SAA in 5/6Nx rats. The rats were injected with SAA (2.5, 5, and 10 mg·kg-1·d-1, ip) for 28 days. Biochemical, flow cytometry, and Western blot analyses showed that SAA significantly increased the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GPx), and catalase (CAT) and lowered the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and NADPH oxidase 4 (NOX-4) in a dose-dependent manner in 5/6Nx rats and in H2O2-induced HK-2 cells in vitro. Moreover, SAA enhanced the activation of the protein kinase B/glycogen synthase kinase-3β/nuclear factor-erythroid-2-related factor 2 (Akt/GSK-3β/Nrf2) signaling pathway in a dose-dependent manner and subsequently increased the expression of heme oxygenase-1 (HO-1) in the kidney of 5/6Nx rats, which were consistent with those obtained in H2O2-induced HK-2 cells in vitro shown by Western blot analysis. Furthermore, SAA significantly increased the expression of intranuclear Nrf2 and HO-1 proteins compared to HK-2 cells stimulated by LPS on the one hand, which can be enhanced by QNZ to some extent; on the other hand, SAA significantly lowered the expression of p-NF-κB p65 and ICAM-1 proteins compared to HK-2 cells stimulated by H2O2, which can be abrogated by ML385 to some extent. In conclusion, our results demonstrated that SAA effectively protects the kidney against oxidative stress in 5/6Nx rats. One of the pivotal mechanisms for the protective effects of SAA on kidney injury was mainly related with its antioxidative roles by activating the Akt/GSK-3β/Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway.

l-carnitine protects human hepatocytes from oxidative stress-induced toxicity through Akt-mediated activation of Nrf2 signaling pathway

2016 ◽  
Vol 94 (5) ◽  
pp. 517-525 ◽  
Author(s):  
Jinlian Li ◽  
Yanli Zhang ◽  
Haiyun Luan ◽  
Xuehong Chen ◽  
Yantao Han ◽  
...  
Keyword(s):  
Protective Effect ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Cell Damage ◽  
Binding Activity ◽  
Akt Pathway ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Akt Inhibitor ◽  
Nrf2 Signaling Pathway

In our previous study, l-carnitine was shown to have cytoprotective effect against hydrogen peroxide (H2O2)-induced injury in human normal HL7702 hepatocytes. The aim of this study was to investigate whether the protective effect of l-carnitine was associated with the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) pathway. Our results showed that pretreatment with l-carnitine augmented Nrf2 nuclear translocation, DNA binding activity and heme oxygenase-1 (HO-1) expression in H2O2-treated HL7702 cells, although l-carnitine treatment alone had no effect on them. Analysis using Nrf2 siRNA demonstrated that Nrf2 activation was involved in l-carnitine-induced HO-1 expression. In addition, l-carnitine-mediated protection against H2O2 toxicity was abrogated by Nrf2 siRNA, indicating the important role of Nrf2 in l-carnitine-induced cytoprotection. Further experiments revealed that l-carnitine pretreatment enhanced the phosphorylation of Akt in H2O2-treated cells. Blocking Akt pathway with inhibitor partly abrogated the protective effect of l-carnitine. Moreover, our finding demonstrated that the induction of Nrf2 translocation and HO-1 expression by l-carnitine directly correlated with the Akt pathway because Akt inhibitor showed inhibitory effects on the Nrf2 translocation and HO-1 expression. Altogether, these results demonstrate that l-carnitine protects HL7702 cells against H2O2-induced cell damage through Akt-mediated activation of Nrf2 signaling pathway.

scholarly journals Phytochemicals protect L02 cells against hepatotoxicity induced by emodin via the Nrf2 signaling pathway

2019 ◽  
Vol 8 (6) ◽  
pp. 1028-1034
Author(s):  
Yan Yan ◽  
Kang Wang ◽  
Xu Tang ◽  
Jun-feng Gao ◽  
Bin-yu Wen
Keyword(s):  
Bile Acid ◽  
Protein Expression ◽  
Protective Effect ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Pharmaceutical Preparations ◽  
Related Factor ◽  
Dependent Manner ◽  
Nrf2 Signaling Pathway ◽  
L02 Cells

Abstract Dihydromyricetin (DMY), hyperoside and silybin are phytochemicals that belong to a class called flavonoids, and they have been used in liver protection pharmaceutical preparations, but the specific mechanism of these chemicals is still unclarified. This study aims to investigate the hepatoprotective effects and potential mechanism of these phytochemicals. The immortalized human hepatocyte cell line L02 was treated with 200 μM emodin for 48 h, and this was used as a hepatocyte injury model. The L02 cells were treated with both 200 μM emodin and different concentrations of DMY/hyperoside/silybin for 48 h to investigate the protective effects of these phytochemicals. The CCK-8 assay was used to detect cell viability. RT-qPCR and western blotting were performed to examine the mRNA and protein expression, respectively, of the classic bile acid synthetic pathway gene CYP7A1, the bile acid efflux transporter bile salt export pump (BSEP), the nuclear factor erythroid-2-related factor 2 (Nrf2) and the drug processing gene CYP1A2. DMY, hyperoside and silybin prevented the impairment of cell viability that was caused by emodin-induced hepatotoxicity in a dose-dependent manner, and at a low concentration (10 μM), the protective effect followed the order hyperoside > DMY > silybin, while at a high concentration (160 μM), the protective effect followed the order DMY > hyperoside > silybin. These phytochemicals reduced the expression of CYP7A1 at both the mRNA and protein levels. BSEP was not influenced by the phytochemical intervention. When 200 μM emodin was used for 48 h with the addition of the phytochemicals at 200 μM, the nuclear protein expression of Nrf2 significantly increased and CYP1A2 expression decreased. DMY, hyperoside and silybin prevented the hepatotoxicity induced by emodin in the L02 cells, potentially, via the Nrf2 signaling pathway.

Sign in / Sign up

Export Citation Format

Share Document