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Hydrogen sulfide pretreatment improves mitochondrial function in myocardial hypertrophy via a SIRT3 dependent manner.

Authors: Meng, Guoliang  Liu, Jieqiong  Liu, Shangmin  Song, Qiuyi  Liu, Lulu  Xie, Liping  Han, Yi  Ji, Yong 
Citation: Meng G, etal., Br J Pharmacol. 2017 May 15. doi: 10.1111/bph.13861.
Pubmed: (View Article at PubMed) PMID:28503736
DOI: Full-text: DOI:10.1111/bph.13861

BACKGROUND AND PURPOSE Hydrogen sulfide (H2 S) is a gaseous signal molecule with anti-oxidative ability. Sirtuin 3 (SIRT3) is closely associated with mitochondrial function and oxidative stress. The study was to investigate whether and how H2 S improved myocardial hypertrophy via a SIRT3-dependent manner. EXPERIMENTAL APPROACH Neonatal rat cardiomyocytes were pre-treated with NaHS (50 µM) for 4 h followed by angiotensin II (Ang II, 100 nM) for 24 h. SIRT3 was silenced with siRNA technology. SIRT 3 promoter activity and expression, cell surface, hypertrophic gene mRNA expression, mitochondrial oxygen consumption rate and membrane potential were measured. Male 129S1/SvImJ (WT) and SIRT3 KO mice were intraperitoneally injected with NaHS (50 µmol/kg/d) followed by transverse aortic constriction (TAC). Echocardiography, heart mass, mitochondrial ultrastructure, volume and number, oxidative stress, mitochondria fusion and fission related protein expression were measured. KEY RESULTS In vitro, NaHS promoted SIRT3 promoter activity and SIRT3 expression in Ang II-induced cardiomyocyte hypertrophy. SIRT3 silencing abolished the ability of NaHS to reverse the Ang II-induced cardiomyocytes hypertrophy, mitochondrial function impairment and permeability potential dysfunction, as well as FOXO3a and SOD2 expression decline. In vivo, NaHS attenuated myocardial hypertrophy, inhibited oxidative stress, improved mitochondrial ultrastructure, suppressed mitochondrial volume but increased mitochondrial numbers, enhanced OPA1, MFN1 and MFN2 expression but suppressed DRP1 and FIS1 expression in WT mice but not in SIRT3 KO mice after TAC. CONCLUSION AND IMPLICATIONS NaHS improved mitochondrial function and inhibited oxidative stress in myocardial hypertrophy via a SIRT3 dependent manner.

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CRRD Object Information
CRRD ID: 12910714
Created: 2017-06-21
Species: All species
Last Modified: 2017-06-21
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.