多硫化物
糖尿病性心肌病
过氧化物酶体
过氧化物酶体增殖物激活受体
锡尔图因
西妥因1
心肌病
氧化应激
下调和上调
自噬
内科学
内分泌学
心力衰竭
化学
医学
细胞生物学
受体
生物
生物化学
细胞凋亡
酶
NAD+激酶
电极
物理化学
电解质
基因
作者
Siping Xiong,Hai‐Jian Sun,Xu Cao,Zhiyuan Wu,Mengyuan Zhu,Lei Cao,Xiaowei Nie,Jin‐Song Bian
标识
DOI:10.1089/ars.2022.0024
摘要
Aims: Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and heart failure. However, the effective therapy for DCM is still lacking. Polysulfide contains chains of sulfur atoms, and accumulative evidence has shown that it actively participates in mammalian physiology or pathophysiology. Nevertheless, the potential effects and mechanisms of polysulfide in DCM need further investigation. In the present study, Na2S4, a polysulfide donor, was employed to investigate the therapeutic effects of polysulfide in DCM. Results: Our results showed that Na2S4 protected cardiomyocytes against high glucose (HG)-induced cardiomyocyte injury. The pathological changes in DCM including cell death, oxidative stress, mitochondrial dysfunction and cardiac hypertrophy were improved by Na2S4 treatment. The left ventricular contractile function in streptozotocin (STZ)-induced diabetic mice was significantly improved by Na2S4. Mechanistically, Na2S4 upregulated and sulfhydrated peroxisome proliferator-activated receptor-γ (PPARγ) and sirtuin 3 (SIRT-3) in cardiomyocytes. Suppression of PPARγ or SIRT-3 with their specific inhibitors or blockade of sulfhydration abolished the protective effects of Na2S4. Moreover, mutations of PPARγ or SIRT-3 at specific cysteines diminished the benefits of Na2S4 in HG-challenged cardiomyocytes. Innovation and Conclusion: We demonstrated that Na2S4 prevented the development of DCM via sulfhydration of both PPARγ and SIRT-3. Our results imply that polysulfide may be a potential and promising agent to treat DCM. Antioxid. Redox Signal. 38, 1–17.
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