scholarly journals Activation of cardiac Nmnat/NAD+/SIR2 pathways mediates endurance exercise resistance to lipotoxic cardiomyopathy in aging Drosophila

2021 ◽  
Vol 224 (18) ◽  
Author(s):  
Deng-tai Wen ◽  
Lan Zheng ◽  
Kai Lu ◽  
Wen-qi Hou
Keyword(s):  
Endurance Exercise ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Sod Activity ◽  
Pathway Activation ◽  
Locomotor Impairment ◽  
Mda Content ◽  
Exercise Induced ◽  
Fractional Shortening ◽  
Lipotoxic Cardiomyopathy

ABSTRACT Endurance exercise is an important way to resist and treat high-fat diet (HFD)-induced lipotoxic cardiomyopathy, but the underlying molecular mechanisms are poorly understood. Here, we used Drosophila to identify whether cardiac Nmnat/NAD+/SIR2 pathway activation mediates endurance exercise-induced resistance to lipotoxic cardiomyopathy. The results showed that endurance exercise activated the cardiac Nmnat/NAD+/SIR2/FOXO pathway and the Nmnat/NAD+/SIR2/PGC-1α pathway, including up-regulating cardiac Nmnat, SIR2, FOXO and PGC-1α expression, superoxide dismutase (SOD) activity and NAD+ levels, and it prevented HFD-induced or cardiac Nmnat knockdown-induced cardiac lipid accumulation, malondialdehyde (MDA) content and fibrillation increase, and fractional shortening decrease. Cardiac Nmnat overexpression also activated heart Nmnat/NAD+/SIR2 pathways and resisted HFD-induced cardiac malfunction, but it could not protect against HFD-induced lifespan reduction and locomotor impairment. Exercise improved lifespan and mobility in cardiac Nmnat knockdown flies. Therefore, the current results confirm that cardiac Nmnat/NAD+/SIR2 pathways are important antagonists of HFD-induced lipotoxic cardiomyopathy. Cardiac Nmnat/NAD+/SIR2 pathway activation is an important underlying molecular mechanism by which endurance exercise and cardiac Nmnat overexpression give protection against lipotoxic cardiomyopathy in Drosophila.

scholarly journals Cardiac Nmnat/NAD+/SIR2 pathways activation mediates endurance exercise resistance to heart defects induced by a high-fat diet in aging Drosophila

2021 ◽  
Author(s):  
Deng-tai Wen ◽  
Lan Zheng ◽  
Kai Lu ◽  
Wen-qi Hou
Keyword(s):  
Endurance Exercise ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Heart Defects ◽  
High Fat ◽  
Sod Activity ◽  
Locomotor Impairment ◽  
Mda Content ◽  
Fractional Shortening

AbstractEndurance exercise is an important way to resist and treat a high-fat-diet(HFD)-induced heart defects, but the underlying molecular mechanisms are poorly understood. Here, we used Drosophila to identify whether cardiac Nmnat/NAD+/SIR2 pathways activation could mediate endurance exercise resistance to heart defects. The results showed that endurance exercise activated the cardiac Nmnat/NAD+/SIR2/FOXO pathway and Nmnat/NAD+/SIR2/PGC-1α pathway, including up-regulating cardiac Nmnat, SIR2, FOXO, PGC-1α expression, SOD activity, and NAD+ level, and it prevented HFD-induced or cardiac Nmnat knock-down-induced cardiac lipid accumulation, MDA content and fibrillation increase, and fractional shortening decrease. Cardiac Nmnat overexpression activated heart Nmnat/NAD+/SIR2 pathways and resisted HFD-induced cardiac malfunction, but it could not protect against HFD-induced lifespan reduction and locomotor impairment. Exercise improved lifespan and mobility in cardiac Nmnat knockdown flies. Therefore, current results confirmed that cardiac Nmnat/NAD+/SIR2 pathways were important antagonists of HFD-induced heart defects. The cardiac Nmnat/NAD+/SIR2 pathways activation was the important underlying molecular mechanism of endurance exercise and cardiac Nmnat overexpression against heart defects in Drosophila.

scholarly journals Endurance exercise resistance to lipotoxic cardiomyopathy is associated with cardiac NAD+/dSIR2/PGC-1α pathway activation in old Drosophila

Biology Open ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. bio044719
Author(s):  
Deng-Tai Wen ◽  
Lan Zheng ◽  
Jin-xiu Li ◽  
Dan Cheng ◽  
Yang Liu ◽  
...  
Keyword(s):  
Endurance Exercise ◽  
Pathway Activation ◽  
Lipotoxic Cardiomyopathy

Sufentanil Affects High Glucose-Induced Oxidative Stress in and Apoptosis of Cardiomyocytes by Regulation of miR-142-3p Expression

2021 ◽  
Vol 11 (3) ◽  
pp. 466-470
Author(s):  
Zhiyong Liu ◽  
Cuiqing Ding ◽  
Changqing Yao ◽  
Jinhui Chen
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Sod Activity ◽  
Apoptosis Rate ◽  
Mda Content

To explore the effects and molecular mechanisms of sufentanil on high glucose-induced oxidative stress in and apoptosis of cardiomyocytes, cardiomyocytes H9c2 cells were classified into groups based on different treatments as high-glucose (HG), HG with low, medium, or high-dose sufentanil, HG with high-dose sufentanil and anti-miR-NC, HG with high-dose sufentanil and anti-miR-142-3p, and control. The cells’ superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected using respective kits. The apoptosis rate in each group was detected by flow cytometry. The expressions of cleaved caspase-3 and pro-caspase3 were determined using western blotting. The expression of miR-142-3p in cardiomyocytes was detected using real-time fluorescent quantitative PCR. Compared with the control group, the HG group had decreased SOD activity, pro-caspase-3 expression, and miR-142-3p expression and increased MDA content, apoptosis, and cleaved caspase-3 expression (P < 0.05). Compared with the HG group, the SOD activity and pro-caspase-3 expression increased and the MDA content, apoptosis rate, and cleaved caspase-3 expression decreased in HG cells treated with low, medium, or high-dose sufentanil. The expression of miR-142-3p was increased in a dose-dependent manner (P < 0.05). The interference of miR-142-3p reversed the effect of sufentanil on high glucose-induced oxidative stress in and apoptosis of cardiomyocytes. Sufentanil may inhibit high glucose-induced oxidative stress in and apoptosis of cardiomyocytes by upregulating miR-142-3p expression.

scholarly journals Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Louise Y. Takeshita ◽  
Peter K. Davidsen ◽  
John M. Herbert ◽  
Philipp Antczak ◽  
Matthijs K. C. Hesselink ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Molecular Mechanisms ◽  
Calcium Signalling ◽  
Sensitivity Index ◽  
Transcriptional Signature ◽  
Endurance Exercise Training ◽  
Causative Effect ◽  
Exercise Induced

AbstractDespite good adherence to supervised endurance exercise training (EET), some individuals experience no or little improvement in peripheral insulin sensitivity. The genetic and molecular mechanisms underlying this phenomenon are currently not understood. By investigating genome-wide variants associated with baseline and exercise-induced changes (∆) in insulin sensitivity index (Si) in healthy volunteers, we have identified novel candidate genes whose mouse knockouts phenotypes were consistent with a causative effect on Si. An integrative analysis of functional genomic and transcriptomic profiles suggests genetic variants have an aggregate effect on baseline Si and ∆Si, focused around cholinergic signalling, including downstream calcium and chemokine signalling. The identification of calcium regulated MEF2A transcription factor as the most statistically significant candidate driving the transcriptional signature associated to ∆Si further strengthens the relevance of calcium signalling in EET mediated Si response.

Evaluation of Azadirachtin on Arthrospira plantensis Gomont growth parameters and antioxidant enzymes

2020 ◽  
Vol 56 ◽  
pp. 8
Author(s):  
Hatice Tunca ◽  
Ali Doğru ◽  
Feray Köçkar ◽  
Burçin Önem ◽  
Tuğba Ongun Sevindik
Keyword(s):  
Enzyme Activity ◽  
Growth Parameters ◽  
Arthrospira Platensis ◽  
Proline Content ◽  
Enzyme Analysis ◽  
Free Proline ◽  
Sod Activity ◽  
Pesticide Pollution ◽  
Antioxidant Parameters ◽  
Mda Content

Azadirachtin (Aza) used as insecticide due to inhibiting growth of insects and preventing them from feeding on plants. To understand the effects of contamination of this insecticide on phototrophs, and to determine the responses of these organisms against these insecticides are extremely important in understanding how the ecosystem is affected. In this study, chlorophyll-a amount, OD 560 and antioxidant parameters (total SOD, APX, GR, Proline, MDA and H2O2) were determined in order to understand the effect of Aza on Arthrospira platensis Gomont. Aza was applied between 0–20 μg mL−1 concentrations for 7 days in the study. Enzyme analysis was conducted at the end of the 7th day. There was a statistically significant decrease in the absorbance of OD560 and the chlorophyll-a content in A. platensis cultures exposed to the Aza (0–20 μg mL−1) during 7 days due to the increase in pesticide levels. SOD activity decreased at 8, 16 and 20 μg mL−1 concentrations; GR enzyme activity showed a significant decrease compared to the control at a concentration of 20 μg mL−1. APX activity did not change significantly compared to control. The MDA content increased significantly at 16 and 20 μg mL−1 concentrations. The H2O2 content significantly increased at 12, 16 and 20 μg mL−1 concentrations (p < 0.05) while the free proline content decreased at 4 μg mL−1 concentration (p < 0.05). As a result, regarding the Aza concentrations used in this study may be a step to prevent pesticide pollution in the environment.

scholarly journals Keap1/Nrf2 pathway activation leads to a repressed hepatic gluconeogenic and lipogenic program in mice on a high-fat diet

2016 ◽  
Vol 591 ◽  
pp. 57-65 ◽  
Author(s):  
Stephen L. Slocum ◽  
John J. Skoko ◽  
Nobunao Wakabayashi ◽  
Susan Aja ◽  
Masayuki Yamamoto ◽  
...  
Keyword(s):  
High Fat Diet ◽  
High Fat ◽  
Nrf2 Pathway ◽  
Pathway Activation

scholarly journals Baicalin Attenuates High Fat Diet-Induced Obesity and Liver Dysfunction: Dose-Response and Potential Role of CaMKKβ/AMPK/ACC Pathway

2015 ◽  
Vol 35 (6) ◽  
pp. 2349-2359 ◽  
Author(s):  
Youli Xi ◽  
Miaozong Wu ◽  
Hongxia Li ◽  
Siqi Dong ◽  
Erfei Luo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Liver Steatosis ◽  
Serum Levels ◽  
Whole Body ◽  
Therapeutic Effects ◽  
High Fat ◽  
Dependent Protein

Background/Aims: Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms. Methods: High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated. Results: Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway. Conclusion: These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKβ/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.

Protective Effects of Ginsenosides on 17α-Ethynyelstradiol-Induced Intrahepatic Cholestasis via Anti-Oxidative and Anti-Inflammatory Mechanisms in Rats

2017 ◽  
Vol 45 (08) ◽  
pp. 1613-1629 ◽  
Author(s):  
Yan-Jiao Xu ◽  
Zao-Qin Yu ◽  
Cheng-Liang Zhang ◽  
Xi-Ping Li ◽  
Cheng-Yang Feng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alkaline Phosphatase ◽  
Superoxide Dismutase ◽  
Protein Expression ◽  
Intrahepatic Cholestasis ◽  
Serum Levels ◽  
Total Bile Acid ◽  
Protective Effects ◽  
Sod Activity ◽  
Mda Content

The present study was designed to assess the effects and potential mechanisms of ginsenosides on 17[Formula: see text]-ethynyelstradiol (EE)-induced intrahepatic cholestasis (IC). Ginsenoside at doses of 30, 100, 300[Formula: see text]mg/kg body weight was intragastrically (i.g.) given to rats for 5 days to examine the effect on EE-induced IC. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bile acid (TBA) were measured. Hepatic malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were determined. Protein expression of proinflammatory cytokines TNF-[Formula: see text], IL-6 and IL-1[Formula: see text] was analyzed by immunohistochemistry and Western blot. Results indicated that ginsenosides remarkably prevented EE-induced increase in the serum levels of AST, ALT, ALP and TBA. Moreover, the elevation of hepatic MDA content induced by EE was significantly reduced, while hepatic SOD activities were significantly increased when treated with ginsenosides. Histopathology of the liver tissue showed that pathological injuries were relieved after treatment with ginsenosides. In addition, treatment with ginsenosides could significantly downregulate the protein expression of TNF-[Formula: see text], IL-6 and IL-1[Formula: see text] compared with EE group. These findings indicate that ginsenosides exert the hepatoprotective effect on EE-induced intrahepatic cholestasis in rats, and this protection might be attributed to the attenuation of oxidative stress and inflammation.

scholarly journals Induction of soluble platelet activation markers and FXIII deficiency promote COVID-19 severity

2021 ◽  
Author(s):  
Abaher O. Al-Tamimi ◽  
Ayesha M. Yusuf ◽  
Manju N. Jayakumar ◽  
Abdul W. Ansari ◽  
Mona Elhassan ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Platelet Activation ◽  
Molecular Mechanisms ◽  
Plasminogen Activator Inhibitor ◽  
Cd40 Ligand ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activation Markers ◽  
Pathway Activation ◽  
Coagulation Dysfunction ◽  
Fxiii Deficiency

Coagulation dysfunction and thromboembolism emerge as strong comorbidity factors in severe COVID-19 patients. However, the underlying pathomechanisms are largely undefined. Here, we sought to identify the potential molecular mechanisms of SARS-CoV-2 mediated coagulopathy and thromboembolism. A broader investigation was conducted including hospitalized COVID-19 patients with (severe cases that required intensive care) or without pneumonia (moderate cases). Phenotypic and molecular characterizations were performed employing basic coagulation tests, flow cytometry-based multiplex assays, and ELISA. The investigations revealed induction of plasma P-selectin and CD40 ligand (sCD40L) in moderate COVID-19 cases which were significantly abolished with the progression of COVID-19 severity. Moreover, a profound reduction in plasma tissue factor pathway inhibitor (TFPI) and FXIII were identified particularly in the severe COVID-19. Further analysis revealed a profound induction of fibrinogen in both moderate and severe patients. Interestingly, an elevated plasminogen activator inhibitor-1 more prominently in moderate, and tissue plasminogen activator (tPA) particularly in severe COVID-19 cases were observed. Particularly, the levels of fibrinogen and tPA directly correlated with the severity of COVID-19. In summary, SARS-CoV-2 infection induces the levels of platelet activation markers soluble P-selectin and sCD40L in hospitalized COVID-19 patients. Furthermore, an attenuated level of TFPI indicates TF pathway activation and, acquired FXIII deficiency likely plays a key role in thrombus instability and promotes thromboembolism in severe cases. The progression of COVID-19 severity could be limited with anti-platelet in combination with recombinantTFPI treatment. Furthermore, thromboembolic events in severe COVID-19 patients could be minimized if treated with recombinantFXIII in combination with LMW heparin.

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