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Hydrogen Sulfide Up-Regulates the Expression of ATP-Binding Cassette Transporter A1 via Promoting Nuclear Translocation of PPARα.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2016 Apr 29; Vol. 17 (5). Date of Electronic Publication: 2016 Apr 29. - Publication Year :
- 2016
-
Abstract
- ATP binding cassette transporter A1 (ABCA1) plays a key role in atherogenesis. Hydrogen sulfide (H₂S), a gasotransmitter, has been reported to play an anti-atherosclerotic role. However, the underlying mechanisms are largely unknown. In this study we examined whether and how H₂S regulates ABCA1 expression. The effect of H₂S on ABCA1 expression and lipid metabolism were assessed in vitro by cultured human hepatoma cell line HepG2, and in vivo by ApoE(-/-) mice with a high-cholesterol diet. NaHS (an exogenous H₂S donor) treatment significantly increased the expression of ABCA1, ApoA1, and ApoA2 and ameliorated intracellular lipid accumulation in HepG2 cells. Depletion of the endogenous H₂S generator cystathionine γ-lyase (CSE) by small RNA interference (siRNA) significantly decreased the expression of ABCA1 and resulted in the accumulation of lipids in HepG2 cells. In vivo NaHS treatment significantly reduced the serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL), diminished atherosclerotic plaque size, and increased hepatic ABCA1 expression in fat-fed ApoE(-/-) mice. Further study revealed that NaHS upregulated ABCA1 expression by promoting peroxisome proliferator-activated receptor α (PPARα) nuclear translocation. H₂S up-regulates the expression of ABCA1 by promoting the nuclear translocation of PPARα, providing a fundamental mechanism for the anti-atherogenic activity of H₂S. H₂S may be a promising potential drug candidate for the treatment of atherosclerosis.
- Subjects :
- ATP Binding Cassette Transporter 1 genetics
Animals
Apolipoprotein A-I genetics
Apolipoprotein A-I metabolism
Apolipoprotein A-II genetics
Apolipoprotein A-II metabolism
Apolipoproteins E deficiency
Apolipoproteins E genetics
Cell Nucleus metabolism
Cell Survival drug effects
Cholesterol blood
Cystathionine gamma-Lyase antagonists & inhibitors
Cystathionine gamma-Lyase genetics
Cystathionine gamma-Lyase metabolism
Diet, High-Fat
Hep G2 Cells
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
PPAR alpha antagonists & inhibitors
Plaque, Atherosclerotic prevention & control
RNA Interference
Triglycerides blood
ATP Binding Cassette Transporter 1 metabolism
Hydrogen Sulfide pharmacology
PPAR alpha metabolism
Up-Regulation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 17
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 27136542
- Full Text :
- https://doi.org/10.3390/ijms17050635