Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0011860 (
type 2 diabetes
)
57,723
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Exogenous H
2
S reduces the acetylation levels of mitochondrial respiratory enzymes via regulating the NAD
+
-SIRT3 pathway in cardiac tissues of
db/db
mice. 3118 32
