Growth differentiation factor-15 induces expression of ATP-binding cassette transporter A1 through PI3-K/PKCζ/SP1 pathway in THP-1 macrophages

被引：18

作者：

Wu, Jian-Feng ^{[1
,2
]}

Wang, Yan ^{[1
,3
]}

Zhang, Min ^{[2
]}

Tang, Yan-Yan ^{[2
]}

Wang, Bo ^{[1
]}

He, Ping-Ping ^{[2
]}

Lv, Yun-Cheng ^{[2
]}

Ouyang, Xin-Ping ^{[2
]}

Yao, Feng ^{[2
]}

Tan, Yu-Lin ^{[2
]}

Tang, Shi-Lin ^{[4
]}

Tang, Deng-Pei ^{[5
]}

Cayabyab, Francisco S. ^{[6
]}

Zheng, Xi-Long ^{[7
]}

Zhang, Da-Wei ^{[8
,9
]}

Zeng, Gao-Feng ^{[1
]}

Tang, Chao-Ke ^{[2
]}

机构：

[1] Univ South China, Affiliated Hosp 2, Dept Cardiovasc Med, Hengyang 421001, Hunan, Peoples R China

[2] Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China

[3] Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Hunan, Peoples R China

[4] Univ South China, Affiliated Hosp 2, Dept Intens Care Unit, Hengyang 421001, Hunan, Peoples R China

[5] Univ Saskatchewan, Dept Biochem, Saskatoon, SK S7H 5E5, Canada

[6] Univ Saskatchewan, Dept Physiol, Saskatoon, SK 57H 5E5, Canada

[7] Univ Calgary, Hlth Sci Ctr, Libin Cardiovasc Inst Alberta, Dept Biochem & Mol Biol, Calgary, AB 72N 4N1, Canada

[8] Univ Alberta, Dept Pediat, Edmonton, AB T6G 2S2, Canada

[9] Univ Alberta, Grp Mol & Cell Biol Lipids, Edmonton, AB T6G 2S2, Canada

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2014年 / 444卷 / 03期

关键词：

GDF-15; Cholesterol efflux; ABCA1; Atherosclerosis; LIVER X RECEPTOR; CHOLESTEROL EFFLUX; SIGNALING PATHWAY; ABCA1; EXPRESSION; LXR-ALPHA; PROTECTS; ATHEROSCLEROSIS; ACTIVATION; INDUCTION; CYTOKINE;

D O I：

10.1016/j.bbrc.2014.01.048

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Objective: The aim of this study was to determine whether ATP-binding cassette transporter A1 (ABCA1) was up-regulated by growth differentiation factor-15 (GDF-15) via the phosphoinositide 3-kinase (PI3K)/protein kinase C zeta (PKc zeta)/specificity protein 1 (SP1) pathway in THP-1 macrophages. Methods and results: We investigated the effects of different concentrations of GDF-15 on ABCA1 expression in THP-1 macrophages. The results showed that GDF-15 dramatically increased cholesterol efflux and decreased cellular cholesterol levels. In addition, GDF15 increased ABCA1 mRNA and protein levels. The effects of GDF-15 on ABCA1 protein expression and cellular cholesterol efflux were abolished by wither inhibition or depletion of PI3K, PKC zeta and SP1, respectively, suggesting the potential roles of PI3K, PKC zeta and SP1 in ABCA1 expression. Taken together, GDF-15 appears to activate PI3K, PKq and SP1 cascade, and then increase ABCA1 expression, thereby promoting cholesterol efflux and reducing foam cell formation. Conclusion: Our results suggest that GDF-15 has an overall protective effect on the progression of atherosclerosis, likely through inducing ABCA1 expression via the PI3K/PKC zeta/SP1 signaling pathway and enhancing cholesterol efflux. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：325 / 331

页数：7

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