miR-503 Is Involved in the Protective Effect of Phase II Enzyme Inducer (CPDT) in Diabetic Cardiomyopathy via Nrf2/ARE Signaling Pathway

Diabetic cardiomyopathy (DCM) is a common heart disease. The Phase II enzyme inducer (CPDT) is a complex enzyme that promotes the expression of antioxidant enzymes through activating nuclear factor erythroid 2-related factor 2 (Nrf2); these compounds have been shown to protect against oxidative stress. However, whether these compounds have similar protective effects in DCM still remains unclear. The purpose of this study is to investigate the protective effects and potential mechanism of CPDT in diabetic cardiomyopathy. In the results, firstly, compared with control rats, myocardial cell size, left ventricular mass index, and myocardial apoptosis index were increased, miR-503 was increased, and Nrf2, malondialdehyde (MDA), and heme oxygenase 1 (HO-1) were decreased in diabetic cardiomyopathy rats. Furthermore, compared with diabetic cardiomyopathy rats, these above parameters show the opposite change in CPDT treatment rats. In addition, the bioinformatics and luciferase reporter assay demonstrated that Nrf2 is a direct target of miR-503. Finally, the miR-503 could also regulate Nrf2 in the myocardial cells. Therefore, miR-503 is involved in the protective effect of CPDT in diabetic cardiomyopathy via Nrf2/ARE signaling pathway; miR-503 and Nrf2 may be a promising therapeutic target for the management of diabetic cardiomyopathy.

Download Full-text

Astragaloside IV Exerts a Myocardial Protective Effect against Cardiac Hypertrophy in Rats, Partially via Activating the Nrf2/HO-1 Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/4625912 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 9

Author(s):

Pei Nie ◽

Fanjing Meng ◽

Jinguo Zhang ◽

Xiqing Wei ◽

Cheng Shen

Keyword(s):

Cardiac Hypertrophy ◽

Protective Effect ◽

Signaling Pathway ◽

Left Ventricular ◽

Cardiomyocyte Hypertrophy ◽

Heme Oxygenase 1 ◽

High Dose ◽

Related Factor ◽

Ang Ii ◽

Astragaloside Iv

Previous evidence suggested that astragaloside IV (ASIV) had a cardioprotective effect, but the potential mechanisms were undetermined. This study is aimed at validating the prevention of cardiac hypertrophy in chronic heart failure (CHF) rats and hypertrophy in H9c2 cardiomyocytes by ASIV and at exploring the potential mechanism involved. CHF rat models of abdominal aortic constriction (AAC) were used with the aim of determining the protective effect of ASIV in cardiac hypertrophy in the rats. We proved that ASIV could attenuate cardiac hypertrophy by improving left ventricular function and structure and showed that the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and its downstream gene heme oxygenase-1 (HO-1) increased in the high-dose ASIV intervention group. To further investigate the specific mechanism of ASIV, we hypothesized that ASIV might prevent cardiac hypertrophy via activating the Nrf2/HO-1 signaling pathway. We established a cardiomyocyte hypertrophy model induced by angiotensin II (Ang II), which was then transfected with Nrf2 shRNA, to knock down the expression of the Nrf2 gene. We found that the protective effect of ASIV against Ang II-induced cardiomyocyte hypertrophy was abolished in the Nrf2 shRNA transfection group, ultimately aggravating cardiomyocyte hypertrophy induced by Ang II, and it is possible that oxidative stress may be involved in this process. Our results demonstrated that ASIV improved cardiac function and inhibited cardiac hypertrophy by upregulating Nrf2, and this effect was partially achieved by stimulating the Nrf2/HO-1 signaling pathway, suggesting that ASIV could have therapeutic potential for the treatment of cardiac hypertrophy and CHF.

Download Full-text

Protective Effects of Taurine Chloramine on Experimentally Induced Colitis: NFκB, STAT3, and Nrf2 as Potential Targets

Antioxidants ◽

10.3390/antiox10030479 ◽

2021 ◽

Vol 10 (3) ◽

pp. 479

Author(s):

Seong Hoon Kim ◽

Hye-Won Yum ◽

Seung Hyeon Kim ◽

Wonki Kim ◽

Su-Jung Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Parent Compound ◽

Oxidative Stress Marker ◽

Heme Oxygenase 1 ◽

Trinitrobenzene Sulfonic Acid ◽

Protective Effects ◽

Taurine Chloramine ◽

Proinflammatory Mediators ◽

Experimentally Induced

Taurine chloramine (TauCl) is an endogenous anti-inflammatory substance which is derived from taurine, a semi-essential sulfur-containing β-amino acid found in some foods including meat, fish, eggs and milk. In general, TauCl as well as its parent compound taurine downregulates production of tissue-damaging proinflammatory mediators, such as chemokines and cytokines in many different types of cells. In the present study, we investigated the protective effects of TauCl on experimentally induced colon inflammation. Oral administration of TauCl protected against mouse colitis caused by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TauCl administration attenuated apoptosis in the colonic mucosa of TNBS-treated mice. This was accompanied by reduced expression of an oxidative stress marker, 4-hydroxy-2-nonenal and proinflammatory molecules including tumor necrosis factor-α, interleukin-6 and cyclooxygenase-2 in mouse colon. TauCl also inhibited activation of NFκB and STAT3, two key transcription factors mediating proinflammatory signaling. Notably, the protective effect of TauCl on oxidative stress and inflammation in the colon of TNBS-treated mice was associated with elevated activation of Nrf2 and upregulation of its target genes encoding heme oxygenase-1, NAD(P)H:quinone oxidoreductase, glutamate cysteine ligase catalytic subunit, and glutathione S-transferase. Taken together, these results suggest that TauCl exerts the protective effect against colitis through upregulation of Nrf2-dependent cytoprotective gene expression while blocking the proinflammatory signaling mediated by NFκB and STAT3.

Download Full-text

Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6746907 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 12

Author(s):

Kaifeng Li ◽

Mengen Zhai ◽

Liqing Jiang ◽

Fan Song ◽

Bin Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Diabetic Cardiomyopathy ◽

High Glucose ◽

Therapeutic Potential ◽

Ros Generation ◽

Protective Effects ◽

Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

Download Full-text

Antagonizing Effects of Clematis apiifolia DC. Extract against Benzo[a]pyrene-Induced Damage to Human Keratinocytes

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/2386163 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Seung Eun Lee ◽

See-Hyoung Park ◽

Ju Ah Yoo ◽

Kitae Kwon ◽

Ji Woong Kim ◽

...

Keyword(s):

Nuclear Translocation ◽

Human Keratinocytes ◽

Antioxidant Response ◽

Luciferase Reporter ◽

Heme Oxygenase 1 ◽

Protective Effects ◽

Cytochrome P450 1A1 ◽

Independent Manner ◽

Reporter Activity ◽

Aryl Hydrocarbon

Background. Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon present in the atmosphere, has cytotoxic and carcinogenic effects. There have been no reports to demonstrate involvement of Clematis apiifolia DC. extract (CAE) in B[a]P-induced effects. This study was conducted to investigate the effect of CAE on B[a]P-induced effects and to elucidate its mechanism of action in HaCaT human keratinocytes. CAE inhibited aryl hydrocarbon receptor (AhR) signaling by decreasing both XRE reporter activity and expression of cytochrome P450 1A1 (CYP1A1) induced by B[a]P treatment in HaCaT cells. We also found that B[a]P-induced nuclear translocation of AhR and production of reactive oxygen species (ROS) and proinflammatory cytokines were attenuated by CAE treatment. CAE treatment suppressed B[a]P-induced phosphorylation of Src (Tyr416). In addition, dasatinib, a Src inhibitor, also inhibited B[a]P-induced nuclear translocation of AhR, similar to CAE treatment. In addition, CAE activated antioxidant response element (ARE) signaling by increasing ARE luciferase reporter activity and expression of ARE-dependent genes such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2), NAD(P)H dehydrogenase [quinone] 1 (NQO1), and heme oxygenase-1 (HO-1). Nuclear translocation of Nrf2 by CAE was demonstrated by Western blot analysis and immunocytochemistry. The effects of CAE on ARE signaling were attenuated by knockdown of the Nrf2 gene. Inhibition of AhR signaling and activation of antioxidant activity by CAE operated in a reciprocally independent manner as evidenced by AhR and Nrf2 siRNA experiments. These findings indicate that CAE exerts protective effects against B[a]P by inhibiting AhR signaling and activating Nrf2-mediated signaling, suggesting its potential in protection from harmful B[a]P-containing pollutants.

Download Full-text

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

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0305 ◽

2016 ◽

Vol 94 (5) ◽

pp. 517-525 ◽

Cited By ~ 9

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.

Download Full-text

Protective Mechanism of Sulforaphane on Cadmium-Induced Sertoli Cell Injury in Mice Testis via Nrf2/ARE Signaling Pathway

Molecules ◽

10.3390/molecules23071774 ◽

2018 ◽

Vol 23 (7) ◽

pp. 1774 ◽

Cited By ~ 14

Author(s):

Shu-Hua Yang ◽

Li-Hui Yu ◽

Lin Li ◽

Yang Guo ◽

Yi Zhang ◽

...

Keyword(s):

Protein Expression ◽

Protective Effect ◽

Signaling Pathway ◽

Sertoli Cell ◽

Sertoli Cells ◽

Heme Oxygenase 1 ◽

Quinone Oxidoreductase ◽

Expression Levels ◽

Apoptosis Rate ◽

Mrna And Protein Expression

The present study evaluated the mechanism underlying the protective effect of sulforaphane (SFN) on cadmium (Cd)-induced Sertoli cell (TM4 cells) injury in mice. The apoptosis rate of cells in each group was detected by flow cytometry. It was determined the effect of SFN on the expression of downstream molecular targets of Nrf2/ARE axis and on the lipid peroxide content. The related genes involved in the nuclear factor E2-related factor 2(Nrf2)/antioxidant response element (ARE) signaling pathway were evaluated by RT-PCR; for example, the mRNA expression levels of Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase (GSH-Px), quinone oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthetase (γ-GCS), while the protein expression levels were assessed by Western blot. Our results showed that the mRNA and protein expression levels of Nrf2, HO-1, NQO1, GSH-Px, and γ-GCS were increased in various degree when the Sertoli cells were to added different concentrations of SFN. Our results also showed that SFN reduced the apoptosis rate, increased the activity of T-SOD, inhibited the increase of the MDA content caused by Cd. Meanwhile, SFN could increase the mRNA and protein expression levels of Nrf2, HO-1 and NQO1 and reduced the mRNA and protein expression levels of GSH-Px and γ-GCS caused by Cd in Sertoli cells (p < 0.01). Taken together, SFN could improve the antioxidant capacity of Sertoli cells, and exert a protective effect on the oxidative damage and apoptosis of Cd-induced Sertoli cells through the activation of Nrf2/ARE signal transduction pathway.

Download Full-text