Polysulfide Protects Against Diabetic Cardiomyopathy Through Sulfhydration of Peroxisome Proliferator-Activated Receptor-gamma and Sirtuin 3

Xiong, Si-ping1,3; Sun, Hai-jian2,3; Cao, Xu3; Wu, Zhi-yuan3; Zhu, Meng-yuan3; Cao, Lei3; Nie, Xiao-wei3,4,6; Bian, Jin-song3,5,7

2023

10.1089/ars.2022.0024

ANTIOXIDANTS & REDOX SIGNALING   Impact Factor & Quartile

1523-0864

1557-7716

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-gamma (PPAR gamma) and sirtuin 3 (SIRT-3) in cardiomyocytes. Suppression of PPAR gamma or SIRT-3 with their specific inhibitors or blockade of sulfhydration abolished the protective effects of Na2S4. Moreover, mutations of PPAR gamma 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 PPAR gamma and SIRT-3. Our results imply that polysulfide may be a potential and promising agent to treat DCM. Antioxid. Redox Signal. 38, 1-17.

polysulfide diabetic cardiomyopathy oxidative stress mitochondrial dysfunction PPAR gamma SIRT-3

SCI

English

Corresponding

Ministry of Education of Singapore Tier 2[MOE2017-T2-2-029] ; Jiangsu Nature Science Foundation[BK20181185] ; Shenzhen Science and Technology Program[KQTD20200820113040070]

Biochemistry & Molecular Biology ; Endocrinology & Metabolism

Biochemistry & Molecular Biology ; Endocrinology & Metabolism

WOS:000917909700001

MARY ANN LIEBERT, INC

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Sun Yat Sen Univ, Affiliated Hosp 8, Dept Pathol, Shenzhen, Peoples R China
2.China Pharmaceut Univ, Sch Tradit Chinese Pharm, Dept Pharmacognosy, Nanjing, Peoples R China
3.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore, Singapore
4.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen Key Lab Resp Dis, Shenzhen, Peoples R China
5.Southern Univ Sci & Technol, Sch Med, Dept Pharmacol, Shenzhen, Peoples R China
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, The Affiliated Hosp 1, Shenzhen Key Lab Resp Dis, Shenzhen 518020, Peoples R China
7.Southern Univ Sci & Technol, Sch Med, Dept Pharmacol, Shenzhen 518055, Guangdong, Peoples R China

Xiong, Si-ping,Sun, Hai-jian,Cao, Xu,et al. Polysulfide Protects Against Diabetic Cardiomyopathy Through Sulfhydration of Peroxisome Proliferator-Activated Receptor-gamma and Sirtuin 3[J]. ANTIOXIDANTS & REDOX SIGNALING,2023,38(1-3).

Xiong, Si-ping.,Sun, Hai-jian.,Cao, Xu.,Wu, Zhi-yuan.,Zhu, Meng-yuan.,...&Bian, Jin-song.(2023).Polysulfide Protects Against Diabetic Cardiomyopathy Through Sulfhydration of Peroxisome Proliferator-Activated Receptor-gamma and Sirtuin 3.ANTIOXIDANTS & REDOX SIGNALING,38(1-3).

Xiong, Si-ping,et al."Polysulfide Protects Against Diabetic Cardiomyopathy Through Sulfhydration of Peroxisome Proliferator-Activated Receptor-gamma and Sirtuin 3".ANTIOXIDANTS & REDOX SIGNALING 38.1-3(2023).