Exogenous hydrogen sulfide attenuates the development of diabetic cardiomyopathy via the FoxO1 pathway

Ye, Peng; Gu, Yue; Zhu, Yanrong; Chao, Yuelin; Kong, Xiangquan; Luo, Jun; Ren, Xiaohan; Zuo, Guang-Feng; Zhang, Dai‐Min; Chen, Shao‐Liang

doi:10.1002/jcp.26946

Cited by 34 publications

(25 citation statements)

References 48 publications

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“…In the present study, the inhibition of the STAT3/HIF-1α pathway reduced ROS generation, MDA content and NOX2 expression, and increased SOD activity and GSH level, attenuating oxidative stress and promoting the antioxidant defense system. On the other hand, previous studies have suggested that exogenous H 2 S alleviates the development of DCM by inhibiting oxidative stress (52,53). Consistent with these observations, the present study also revealed that GYY4137 pretreatment eliminates HG-induced oxidative stress, which was a similar effect to that of inhibition of the STAT3/HIF-1α pathway.…”

Section: Discussionmentioning

confidence: 95%

Exogenous hydrogen sulfide protects against high glucose‑induced apoptosis and oxidative stress by inhibiting the STAT3/HIF‑1α pathway in H9c2 cardiomyocytes

Yang

Zhang

et al. 2019

Exp Ther Med

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Hydrogen sulfide (H2S), an endogenous gasotransmitter, possesses multiple physiological and pharmacological properties including anti-apoptotic, anti-oxidative stress and cardiac protective activities in diabetic cardiomyopathy. An increasing body of evidence has suggested that signal transducer and activator of transcription 3 (STAT3) has beneficial effects in the heart. However, the effect of diabetes on the phosphorylation or activation of cardiac STAT3 appears to be controversial. The present study was designed to investigate the precise function of the STAT3/hypoxia-inducible factor-1α (HIF-1α) signaling pathway in high glucose (HG)-induced H9c2 cardiomyocyte injury and the function of the STAT3/HIF-1α pathway in the cardioprotective action of H2S. The results revealed that GYY4137 pretreatment substantially ameliorated the HG-induced decrease in cell viability and the increase in lactate dehydrogenase (LDH) release in H9c2 cells. Additionally, HG treatment resulted in the upregulation of the phosphorylated (p)-STAT3/STAT3 ratio and HIF-1α protein expression in H9c2 cells, indicating that the activation of the STAT3/HIF-1α pathway was induced by HG. STAT3/HIF-1α pathway inhibition induced by transfection with STAT3 small interfering (si)-RNA attenuated the HG-induced downregulation of cell viability and the upregulation of LDH release. Furthermore, STAT3 siRNA transfection and GYY4137 pretreatment combined attenuated HG-induced apoptosis as illustrated by the decrease in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, caspase-3 activity, apoptosis ratio and BCL2 associated X, apoptosis regulator/BCL2 apoptosis regulator ratio in H9c2 cells. In addition, STAT3 siRNA transfection and GYY4137 blocked HG-induced oxidative stress as evidenced by the decrease in reactive oxygen species generation, malondialdehyde content and NADPH oxidase 2 expression, and the increase in superoxide dismutase activity and glutathione level. Notably, GYY4137 pretreatment was revealed to reduce the p-STAT3/STAT3 ratio and HIF-1α protein expression, resulting in the inhibition of the STAT3/HIF-1α signaling pathway in HG-treated H9c2 cells. Altogether, the present results demonstrated that H2S mitigates HG-induced H9c2 cell damage, and reduces apoptosis and oxidative stress by suppressing the STAT3/HIF-1α signaling pathway.

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Section: Discussionmentioning

confidence: 95%

Exogenous hydrogen sulfide protects against high glucose‑induced apoptosis and oxidative stress by inhibiting the STAT3/HIF‑1α pathway in H9c2 cardiomyocytes

Yang

Zhang

et al. 2019

Exp Ther Med

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“…FOXO1 is also known as forkhead within the rhabdomyosarcoma, as well as a transcription factor playing an important role in regulation of gluconeogenesis 28, 29. In VSMCs, FOXO1 has been powerfully proven to regulate vascular remodeling and diabetic cardiomyopathy 30, 31. In addition, FOXO1 functions a transcription factor to modulate the human cancers 32 .…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circCHFR Facilitates the Proliferation and Migration of Vascular Smooth Muscle via miR-370/FOXO1/Cyclin D1 Pathway

Yang

Zhao

et al. 2019

Molecular Therapy - Nucleic Acids

116

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Circular RNA (circRNA) is a novel subgroup of noncoding RNA in the human transcriptome playing a vital role in the atherosclerosis of cerebrovascular disease. However, the in-depth mechanism by which circRNA regulates the vascular smooth muscle proliferation and migration is still elusive. Here, a novel identified circRNA, circCHFR, was validated to be aberrantly overexpressed in the ox-LDL-induced vascular smooth muscle cell (VSMCs). Functionally, the circCHFR silencing by oligonucleotide transfection suppressed the proliferation and migration ability of VSMCs. Mechanically, bioinformatics tools and luciferase reporter assay state that circCHFR acts as a sponge of miR-370, and miR-370 targets the 3′ UTR of FOXO1. Furthermore, the transcription factor FOXO1 could bind with the promoter region of CCND1 mRNA and promote Cyclin D1 expression. In summary, this finding states the vital role of the circCHFR/miR-370/FOXO1/Cyclin D1 axis and provides a profound understanding about the circRNA in smooth muscle cells and atherosclerosis.

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“…In turn, Ca 2+ /CaM can regulate the activity of CSE and the formation of H 2 S [102]. Exogenous H 2 S improves cardiac function and attenuates cardiac hypertrophy and myocardial fibrosis in diabetic mice via the forkhead box protein O1 (FOXO1) pathway [112]. This protein plays important roles in the regulation of gluconeogenesis and glycogenolysis by insulin signaling; hence, by increasing exogenous H 2 S, protective effects against diabetic cardiomyopathy are attained.…”

Section: Diarylheptanoidmentioning

confidence: 99%

Nanopolyphenols: a review of their encapsulation and anti-diabetic effects

Rambaran

2020

SN Appl. Sci.

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Polyphenols are believed to possess numerous health benefits and can be grouped as phenolic acids, flavonoids or non-flavonoids. Research involving the synthesis of nanopolyphenols has attracted interest in the areas of functional food, nutraceutical and pharmaceutical development. This is in an effort to overcome current challenges which limit the application of polyphenols such as their rapid elimination, low water-solubility, instability at low pH, and their particle size. In the synthesis of nanopolyphenols, the type of nanocarrier used, the nanoencapsulation technique employed and the type of polymers that constitute the drug delivery system are crucial. For this review, all mentioned factors which can influence the therapeutic efficacy of nanopolyphenols were assessed. Their efficacy as anti-diabetic agents was also evaluated in 33 publications. Among these were phenolic acid (1), flavonoids (13), non-flavonoids (17) and polyphenolrich extracts (2). The most researched polyphenols were quercetin and curcumin. Nanoparticles were the main nanocarrier and the size of the nanopolyphenols ranged from 15 to 333 nm with encapsulation efficiency and drug loading capacities of 56-97.7% and 4.2-53.2%, respectively. The quantity of nanomaterial administered orally ranged from 1 to 300 mg/kg/day with study durations of 1-70 days. Most studies compared the effect of the nanopolyphenol to its freeform and, in all but three cases, significantly greater effects of the former were reported. Assessment of the polyphenol to understand its properties and the subsequent synthesis of its nanoencapsulated form using suitable nanocarriers, polymers and encapsulation techniques can result in effective therapeutic agents for the treatment of diabetes.

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Exogenous hydrogen sulfide attenuates the development of diabetic cardiomyopathy via the FoxO1 pathway

Abstract: Our data indicate that H S is a novel regulator of FoxO1 in cardiac cells and provide evidence supporting the potential of H S in inhibiting the progression of DCM.

Cited by 34 publications

References 48 publications

Exogenous hydrogen sulfide protects against high glucose‑induced apoptosis and oxidative stress by inhibiting the STAT3/HIF‑1α pathway in H9c2 cardiomyocytes

Exogenous hydrogen sulfide protects against high glucose‑induced apoptosis and oxidative stress by inhibiting the STAT3/HIF‑1α pathway in H9c2 cardiomyocytes

Circular RNA circCHFR Facilitates the Proliferation and Migration of Vascular Smooth Muscle via miR-370/FOXO1/Cyclin D1 Pathway

Nanopolyphenols: a review of their encapsulation and anti-diabetic effects

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