Cystathionine γ-lyase(CSE)/hydrogen sulfide system is regulated by miR-216a and influences cholesterol efflux in macrophages via the PI3K/AKT/ABCA1 pathway

Duo Gong; Hai-Peng Cheng; Wei Xie; Min Zhang; Dan Liu; Gang Lan; Chong Huang; Zhen-Wang Zhao; Ling-Yan Chen; Feng Yao; Yu-Lin Tan; Liang Li; Xiao-Dan Xia; Xi-Long Zheng; Zong-Bao Wang; Chao-Ke Tang

doi:10.1016/j.bbrc.2016.01.003

Cystathionine γ-lyase(CSE)/hydrogen sulfide system is regulated by miR-216a and influences cholesterol efflux in macrophages via the PI3K/AKT/ABCA1 pathway

Biochem Biophys Res Commun. 2016 Jan 29;470(1):107-116. doi: 10.1016/j.bbrc.2016.01.003. Epub 2016 Jan 7.

Authors

Duo Gong¹, Hai-Peng Cheng¹, Wei Xie¹, Min Zhang¹, Dan Liu¹, Gang Lan¹, Chong Huang¹, Zhen-Wang Zhao¹, Ling-Yan Chen¹, Feng Yao¹, Yu-Lin Tan¹, Liang Li¹, Xiao-Dan Xia¹, Xi-Long Zheng², Zong-Bao Wang³, Chao-Ke Tang⁴

Affiliations

¹ Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target NewDrug Study, University of South China, Hengyang, Hunan, 421001, China.
² Department of Biochemistry and Molecular Biology, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta, T2N 4N1, Canada.
³ School of Pharmacy and Life Science College, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China. Electronic address: wzbscience@126.com.
⁴ Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target NewDrug Study, University of South China, Hengyang, Hunan, 421001, China. Electronic address: tangchaoke@qq.com.

PMID: 26772887
DOI: 10.1016/j.bbrc.2016.01.003

Abstract

This study was designed to evaluate whether CSE/H2S system, which is regulated by miR-216a, regulated ABCA1-mediated cholesterol efflux and cholesterol contents in THP-1 macrophages-derived foam cells. Our qPCR and western blotting results showed that CSE/H2S significantly up-regulated the expression of ATP-binding cassette transporter A1 (ABCA1) mRNA and protein via PI3K/AKT pathway in foam cells derived from human THP-1 macrophages. The miR-216a directly targeted 3' untranslated region of CSE. It significantly reduced CSE and ABCA1 expression, and also decreased the phosphorylation of PI3K and AKT. Additionally, cholesterol efflux decreased, and cholesterol levels increased in THP-1 macrophage-derived foam cells in response to treatment with miR-216a. Our study demonstrates that CSE/H2S system is regulated by miR-216a, and regulates ABCA1-mediated cholesterol efflux and cholesterol levels through the PI3K/AKT pathway.

Keywords: ABCA1; CSE; Cholesterol efflux; Endogenous H(2)S; PI3K/AKT pathway; miR-216a.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter 1 / metabolism*
Cell Line
Cholesterol / metabolism*
Cystathionine gamma-Lyase / metabolism*
Humans
Hydrogen Sulfide / metabolism*
Macrophages / metabolism*
MicroRNAs / metabolism*
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction / physiology

Substances

ABCA1 protein, human
ATP Binding Cassette Transporter 1
MIRN216 microRNA, human
MicroRNAs
Cholesterol
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Cystathionine gamma-Lyase
Hydrogen Sulfide