In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 317, No. 2 ( 2019-08-01), p. E284-E297
Abstract:
Hydrogen sulfide (H 2 S), a gaseous molecule, is involved in modulating multiple physiological functions, such as antioxidant, antihypertension, and the production of polysulfide cysteine. H 2 S may inhibit reactive oxygen species generation and ATP production through modulating respiratory chain enzyme activities; however, the mechanism of this effect remains unclear. In this study, db/db mice, neonatal rat cardiomyocytes, and H9c2 cells treated with high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. The mitochondrial respiratory rate, respiratory chain complex activities, and ATP production were decreased in db/db mice compared with those in db/db mice treated with exogenous H 2 S. Liquid chromatography with tandem mass spectrometry analysis showed that the acetylation level of proteins involved in the mitochondrial respiratory chain were increased in the db/db mice hearts compared with those with sodium hydrosulfide (NaHS) treatment. Exogenous H 2 S restored the ratio of NAD + /NADH, enhanced the expression and activity of sirtuin 3 (SIRT3) and decreased mitochondrial acetylation level in cardiomyocytes under hyperglycemia and hyperlipidemia. As a result of SIRT3 activation, acetylation of the respiratory complexe enzymes NADH dehydrogenase 1 (ND1), ubiquinol cytochrome c reductase core protein 1, and ATP synthase mitochondrial F1 complex assembly factor 1 was reduced, which enhanced the activities of the mitochondrial respiratory chain activity and ATP production. We conclude that exogenous H 2 S plays a critical role in improving cardiac mitochondrial function in diabetes by upregulating SIRT3.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00326.2018
Language:
English
Publisher:
American Physiological Society
Publication Date:
2019
detail.hit.zdb_id:
1477331-4
SSG:
12
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