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

ACCESS DATA

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

Similar Datasets

Project description:The deacetylase SIRT1 (sirtuin 1) has emerged as a major regulator of nucleocytoplasmic distribution of macroautophagy/autophagy marker MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3). Activation of SIRT1 leads to the deacetylation of LC3 and its translocation from the nucleus into the cytoplasm leading to an increase in the autophagy flux. Notably, hydrogen sulfide (H2S) is a cytoprotective gasotransmitter known to activate SIRT1 and autophagy; however, the underlying mechanism for both remains unknown. Herein, we demonstrate that H2S sulfhydrates the active site cysteine of the glycolytic enzyme GAPDH (glyceraldehyde-3-phosphate dehydrogenase). Sulfhydration of GAPDH leads to its redistribution into the nucleus. Importantly, nuclear localization of GAPDH is critical for H2S-mediated activation of autophagy as H2S does not induce autophagy in cells with GAPDH ablation or cells overexpressing a GAPDH mutant lacking the active site cysteine. Importantly, we observed that nuclear GAPDH interacts with CCAR2/DBC1 (cell cycle activator a nd apoptosis regulator 2) inside the nucleus. CCAR2 interacts with the deacetylase SIRT1 to inhibit its activity. Interaction of GAPDH with CCAR2 disrupts the inhibitory effect of CCAR2 on SIRT1. Activated SIRT1 then deacetylates MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) to induce its translocation into the cytoplasm and activate autophagy. Additionally, we demonstrate this pathway's physiological role in autophagy-mediated trafficking of Mycobacterium tuberculosis into lysosomes to restrict intracellular mycobacteria growth. We think that the pathway described here could be involved in H2S-mediated clearance of intracellular pathogens and other health benefits.Abbreviations: ATG5: autophagy related 5; ATG7: autophagy related 7; BECN1: beclin 1, autophagy related; CCAR2/DBC1: cell cycle activator and apoptosis regulator 2; CFU: colony-forming units; DLG4/PSD95: discs large MAGUK scaffold protein 4; EX-527: 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; H2S: hydrogen sulfide; HEK: human embryonic kidney cells; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MEF: mouse embryonic fibroblast; Mtb: Mycobacterium tuberculosis; MTOR: mechanistic target of rapamycin kinase; MOI: multiplicity of infection; NO: nitric oxide; PI3K: phosphatidylinositol-4,5-bisphosphate 3-kinase; PLA: proximity ligation assay; PRKAA: protein kinase, AMP-activated, alpha catalytic subunit; SIAH1: siah E3 ubiquitin protein ligase 1A; SIRT1: sirtuin 1; TB: tuberculosis; TP53INP2/DOR: transformation related protein 53 inducible nuclear protein 2; TRP53/TP53: transformation related protein 53.

Dataset Information

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

Background and purpose

Experimental approach

Key results

Conclusions and implications

Linked articles

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background and purpose

Experimental approach

Key results

Conclusions and implications

Linked articles

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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