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:C0020473 (
hyperlipidemia
)
15,891
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hydrogen sulfide (H
2
S), an important gasotransmitter, regulates cardiovascular functions. Mitochondrial damage induced by the overproduction of reactive oxygen species (ROS) results in myocardial injury with a diabetic state. The purpose of this study was to investigate the effects of exogenous H
2
S on mitophagy formation in diabetic cardiomyopathy. In this study, we found that exogenous H
2
S could improve cardiac functions, reduce mitochondrial fragments and ROS levels, enhance mitochondrial respiration chain activities and inhibit mitochondrial apoptosis in the hearts of db/db mice. Our results showed that exogenous H
2
S facilitated parkin translocation into mitochondria and promoted mitophagy formation in the hearts of db/db mice. Our studies further revealed that the ubiquitination level of cytosolic parkin was increased and the expression of
USP8
, a deubiquitinating enzyme, was decreased in db/db cardiac tissues. S-sulfhydration is a novel posttranslational modification of specific cysteine residues on target proteins by H
2
S. Our results showed that the S-sulfhydration level of
USP8
was obviously decreased in vivo and in vitro under hyperglycemia and
hyperlipidemia
, however, exogenous H
2
S could reverse this effect and promote
USP8
/parkin interaction. Dithiothreitol, a reducing agent that reverses sulfhydration-mediated covalent modification, increased the ubiquitylation level of parkin, abolished the effects of exogenous H
2
S on
USP8
deubiquitylation and suppressed the interaction of
USP8
with parkin in neonatal rat cardiomyocytes treated with high glucose, oleate and palmitate. Our findings suggested that H
2
S promoted mitophagy formation by increasing S-sulfhydration of
USP8
, which enhanced deubiquitination of parkin through the recruitment of parkin in mitochondria.
...
PMID:Exogenous H
2
S Promoted USP8 Sulfhydration to Regulate Mitophagy in the Hearts of db/db Mice. 3225 41
