Dataset Information

Hydrogen sulfide regulates muscle RING finger-1 protein S-sulfhydration at Cys⁴⁴ to prevent cardiac structural damage in diabetic cardiomyopathy.

ABSTRACT:

Background and purpose

Hydrogen sulfide (H₂ S) plays important roles as a gasotransmitter in pathologies. Increased expression of the E3 ubiquitin ligase, muscle RING finger-1 (MuRF1), may be involved in diabetic cardiomyopathy. Here we have investigated whether and how exogenous H₂ S alleviates cardiac muscle degradation through modifications of MuRF1 S-sulfhydration in db/db mice.

Experimental approach

Neonatal rat cardiomyocytes were treated with high glucose (40 mM), oleate (100 ?M), palmitate (400 ?M), and NaHS (100 ?M) for 72 hr. MuRF1 was silenced with siRNA technology and mutation at Cys⁴⁴ . Endoplasmic reticulum stress markers, MuRF1 expression, and ubiquitination level were measured. db/db mice were injected with NaHS (39 ?mol·kg^-1 ) for 20 weeks. Echocardiography, cardiac ultrastructure, cystathionine-?-lyase, cardiac structure proteins expression, and S-sulfhydration production were measured.

Key results

H₂ S levels and cystathionine-?-lyase protein expression in myocardium were decreased in db/db mice. Exogenous H₂ S reversed endoplasmic reticulum stress, including impairment of the function of cardiomyocytes and structural damage in db/db mice. Exogenous H₂ S could suppress the levels of myosin heavy chain 6 and myosin light chain 2 ubiquitination in cardiac tissues of db/db mice, and MuRF1 was modified by S-sulfhydration, following treatment with exogenous H₂ S, to reduce the interaction between MuRF1 and myosin heavy chain 6 and myosin light chain 2.

Conclusions and implications

Our findings suggest that H₂ S regulates MuRF1 S-sulfhydration at Cys⁴⁴ to prevent myocardial degradation in the cardiac tissues of db/db mice.

Linked articles

This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.

SUBMITTER: Sun X

PROVIDER: S-EPMC7024715 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Hydrogen sulfide regulates muscle RING finger-1 protein S-sulfhydration at Cys<sup>44</sup> to prevent cardiac structural damage in diabetic cardiomyopathy.

Sun Xiaojiao X Zhao Dechao D Lu Fangping F Peng Shuo S Yu Miao M Liu Ning N Sun Yu Y Du Haining H Wang Bingzhu B Chen Jian J Dong Shiyun S Lu Fanghao F Zhang Weihua W

British journal of pharmacology 20190429 4

<h4>Background and purpose</h4>Hydrogen sulfide (H<sub>2</sub> S) plays important roles as a gasotransmitter in pathologies. Increased expression of the E3 ubiquitin ligase, muscle RING finger-1 (MuRF1), may be involved in diabetic cardiomyopathy. Here we have investigated whether and how exogenous H<sub>2</sub> S alleviates cardiac muscle degradation through modifications of MuRF1 S-sulfhydration in db/db mice.<h4>Experimental approach</h4>Neonatal rat cardiomyocytes were treated with high gluc ...[more]

PMID: 30734268

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