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

• Published in: Biochemical and biophysical research communications 2016, Vol.470 (29), p.107-116
• Main Authors: Gong, Duo, 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
• Format: Article
• Language: English
• Subjects: ABC transporters; ABCA1; cholesterol; Cholesterol efflux; CSE; cystathionine; cystathionine gamma-lyase; Endogenous H2S; foam cells; gene expression regulation; humans; messenger RNA; miR-216a; phosphatidylinositol 3-kinase; phosphorylation; PI3K/AKT pathway; quantitative polymerase chain reaction; sulfides; Western blotting
• ISSN: 0006-291X; 1090-2104

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.