1,25(OH)<sub>2</sub>D<sub>3</sub> improves cardiac dysfunction, hypertrophy, and fibrosis through PARP1/SIRT1/mTOR‐related mechanisms in type 1 diabetes

Qu, Hua; Lin, Ke; Wang, Hang; Wei, Huijie; Ji, Baolan; Yang, Zengsong; Peng, Chuan; Xiao, Xiaoqiu; Deng, Hongkui

doi:10.1002/mnfr.201600338

Cited by 40 publications

(28 citation statements)

References 43 publications

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“…Previously, studies have shown that SIRT1 negatively regulated mTOR signaling in a variety of cells, such as MEFs cells, HeLa cells and cardiomyocytes [48,49]. In the current work, we showed that SIRT1 mediated mTOR signaling in response to high glucose in neurons, evidenced by SIRT1 agonist resveratrol inhibited high glucose-induced phosphorylation of mTOR in HT-22 cells.…”

Section: Discussionsupporting

confidence: 57%

Hydrogen Sulfide Ameliorates High Glucose-induced Inflammation Through SIRT1-mTOR/NF-κB Signaling Pathway in HT-22 cells

et al. 2020

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Background: Hyperglycemia-induced neuroinflammation promotes the progression of diabetic encephalopathy (DE). Hydrogen sulfide (H2S) exerts anti-inflammatory and neuroprotective activities against neurodegenerative diseases. However, its role in hyperglycemia-induced neuronal inflammation has not been investigated. Herein, we examined the effects and its related signaling pathway of H2S on inflammatory response in high glucose-treated HT-22 cells.Methods: A hippocampal neuronal cell line, HT-22, was used as an in vitro model to explore the function of H2S on inflammatory response triggered by high glucose. A dicyanoisophorone-based near-infrared fluorescent probe (NIR-NP) was synthesized to detect H2S levels in HT-22 cells. Western blotting, immunofluorescence and real time-qPCR were carried out to study the mechanism of action for H2S.Results: We found that high glucose (85 mM) decreased the level of endogenous H2S and the expression of cystathionine-β-synthase (CBS) which is the main enzyme for H2S production in the brain. Sodium hydrosulfide (NaHS, a H2S donor) or S-adenosylmethionine (SAMe, an allosteric activator of CBS) administration restored high glucose-induced downregulation of CBS and H2S levels. Importantly, high glucose upregulated the level of pro-inflammatory factors (IL-1β, IL-6, TNF-α) in HT-22 cells. Treatment with NaHS or SAMe alleviated this enhanced transcription of these pro-inflammatory factors, suggesting that H2S might ameliorate high glucose-induced inflammation in HT-22 cells. We also found that high glucose reduced SIRT1 protein levels. SIRT1 reduction elevated the level of p-mTOR, p-NF-κB and pro-inflammatory factors, which were restored by resveratrol (a SIRT1 agonist). These results suggested that SIRT1 might be an upstream mediator of mTOR/NF-κB signaling pathway. Furthermore, NaHS or SAMe treatment reversed the expression of SIRT1, mTOR and NF-κB under high glucose conditions.Conclusions: Our study revealed that high glucose decreased CBS to reduce the production of H2S, which in turn decreased the expression of SIRT1. The reduction of SIRT1 activated mTOR/NF-κB signaling to promote inflammation. Given that promoting H2S production using NaHS or SAMe can reverse high glucose-induced inflammatory response, our study might shed light on the prophylactic treatment of DE.

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Section: Discussionsupporting

confidence: 57%

Hydrogen Sulfide Ameliorates High Glucose-induced Inflammation Through SIRT1-mTOR/NF-κB Signaling Pathway in HT-22 cells

et al. 2020

Preprint

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“…Increased expression of connective tissue growth factor (CTGF), TGF-β1, SMAD3, poly [ADP-ribose] polymerase 1 (PARP1), sirtuin 1 (SIRT1), and mechanistic target of rapamycin (mTOR) in diabetes mediate cardiac fibrosis [61–63]. The negative regulation of the activity of TGF-β1, SMAD3, CTGF, and PARP1/SIRT1/mTOR pathway with vitamin D suggests the protective role of vitamin D on fibrosis [63–66](Table 1). Wang et al [67] using the rat model reported that diabetes induces the cardiac weight index, plasma glucose, lactic dehydrogenase and creatine kinase with the reduced body and cardiac weights and pathological changes of fibrosis.…”

Section: Cardiac Diseasesmentioning

confidence: 99%

Role of Vitamin D in Cardiovascular Diseases

Rai

Agrawal

2017

Endocrinology and Metabolism Clinics of North America

118

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Vitamin D is critical in mineral homeostasis and skeletal health, and plays regulatory role in non-skeletal tissues. Vitamin D deficiency is associated with chronic inflammatory diseases, including diabetes and obesity both being strong risk factors for cardiovascular diseases (CVD). CVD, including coronary artery disease, myocardial infarction, hypertrophy, cardiomyopathy, cardiac fibrosis, heart failure, aneurysm, peripheral arterial disease, hypertension, and atherosclerosis, are major causes of morbidity and mortality worldwide. The association of these diseases with vitamin D deficiency and improvement with vitamin D supplementation suggest its therapeutic benefit. Here, we critically review the recent findings on the association of vitamin D deficiency and CVD.

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“…Current evidence shows that association of vitamin D and sirtuins may be through both direct and indirect pathways. Direct association of vitamin D with SIRT1, through vitamin D receptor (VDR), has been shown in experimental models [39][40][41]. On the other hand, vitamin D-induced upregulation of SIRT1 together with pAMPK and GLUT-4 in adipose tissue suggests a role for these insulinindependent signaling molecules in glycemic control through vitamin D [38].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Daily Intake of Vitamin D-Fortified Yogurt Drink, With and Without Added Calcium, on Serum Adiponectin and Sirtuins 1 and 6 in Adult Subjects with Type 2 Diabetes

Nikooyeh

Hollis

Neyestani

2020

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BackgroundThere is evidence suggesting an effect of vitamin D on glycemic status through mediators including adiponectin and sirtuins.ObjectiveTo evaluate the effects of daily intake of vitamin D-fortified yogurt drink, either with or without added calcium, on serum adiponectin, sirtuins (SIRT)1 and 6. DesignBriefly, 75 adults aged 30-60 yrs from both sexes with type 2 diabetes were randomly allocated to one of the three groups: (i) D-fortified-yogurt drink (DY; containing 1000 IU vitamin D and 300 mg calcium), (ii) Ca+D-fortified-yogurt drink (CDY; containing 1000 IU vitamin D and 500 mg calcium) and (iii) plain yogurt drink (PY; containing no detectable vitamin D and 300 mg calcium). All assessments were performed initially and after 12 weeks. ResultsA significant within-group increment in serum adiponectin concentrations was observed in both DY and CDY groups (+60.4± 8.6, +57.5± 6.4 µg/L, respectively; p<0.001 for both). The concentrations of SIRT1 and SIRT6 had a significant within-group increment only in the CDY group (p=0.003, p=0.001 respectively). Being in CDY group was more favorable predictor of improvement in SIRT6 concentrations. Changes of 25(OH)D was a significant predictor of changes of adiponectin. However, this association disappeared following adjustment for changes of SIRT1. In contrast, the association between changes of 25(OH)D and HbA1c remained significant even after adjustment for SIRT1. ConclusionDaily consumption of vitamin D-fortified yogurt drink for 12 weeks resulted in an increase in circulating concentrations of SIRT1 and SIRT6 in T2D subjects and D+Ca-fortified yogurt drink was more in favor of SIRT6 increment.

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1,25(OH)₂D₃ improves cardiac dysfunction, hypertrophy, and fibrosis through PARP1/SIRT1/mTOR‐related mechanisms in type 1 diabetes

Abstract: The present study demonstrates that 1,25(OH) D treatment has the potential to improve diabetic cardiomyopathy in rats and suggests that VD-VDR signaling induces this protective effect against diabetic cardiomyopathy might partly through the PARP1/SIRT1/mTOR pathway.

Cited by 40 publications

References 43 publications

Hydrogen Sulfide Ameliorates High Glucose-induced Inflammation Through SIRT1-mTOR/NF-κB Signaling Pathway in HT-22 cells

Hydrogen Sulfide Ameliorates High Glucose-induced Inflammation Through SIRT1-mTOR/NF-κB Signaling Pathway in HT-22 cells

Role of Vitamin D in Cardiovascular Diseases

The Effect of Daily Intake of Vitamin D-Fortified Yogurt Drink, With and Without Added Calcium, on Serum Adiponectin and Sirtuins 1 and 6 in Adult Subjects with Type 2 Diabetes

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1,25(OH)2D3 improves cardiac dysfunction, hypertrophy, and fibrosis through PARP1/SIRT1/mTOR‐related mechanisms in type 1 diabetes

Abstract: The present study demonstrates that 1,25(OH) D treatment has the potential to improve diabetic cardiomyopathy in rats and suggests that VD-VDR signaling induces this protective effect against diabetic cardiomyopathy might partly through the PARP1/SIRT1/mTOR pathway.

Cited by 40 publications

References 43 publications

Hydrogen Sulfide Ameliorates High Glucose-induced Inflammation Through SIRT1-mTOR/NF-κB Signaling Pathway in HT-22 cells

Hydrogen Sulfide Ameliorates High Glucose-induced Inflammation Through SIRT1-mTOR/NF-κB Signaling Pathway in HT-22 cells

Role of Vitamin D in Cardiovascular Diseases

The Effect of Daily Intake of Vitamin D-Fortified Yogurt Drink, With and Without Added Calcium, on Serum Adiponectin and Sirtuins 1 and 6 in Adult Subjects with Type 2 Diabetes

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1,25(OH)₂D₃ improves cardiac dysfunction, hypertrophy, and fibrosis through PARP1/SIRT1/mTOR‐related mechanisms in type 1 diabetes