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Int. J. Mol. Sci. 2016, 17(5), 635; doi:10.3390/ijms17050635

Hydrogen Sulfide Up-Regulates the Expression of ATP-Binding Cassette Transporter A1 via Promoting Nuclear Translocation of PPARα

1
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
2
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201210, China
3
Improvinglife Biological Technology (Shanghai) Co., Ltd., Shanghai 201210, China
*
Author to whom correspondence should be addressed.
Academic Editor: Michael Henein
Received: 29 February 2016 / Revised: 18 April 2016 / Accepted: 20 April 2016 / Published: 29 April 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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. View Full-Text
Keywords: hydrogen sulfide; atherosclerosis; ABCA1; PPARα hydrogen sulfide; atherosclerosis; ABCA1; PPARα
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Li, D.; Xiong, Q.; Peng, J.; Hu, B.; Li, W.; Zhu, Y.; Shen, X. Hydrogen Sulfide Up-Regulates the Expression of ATP-Binding Cassette Transporter A1 via Promoting Nuclear Translocation of PPARα. Int. J. Mol. Sci. 2016, 17, 635.

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