SDF-1α/CXCR4 decreases endothelial progenitor cells apoptosis under serum deprivation by PI3K/Akt/eNOS pathway

被引：126

作者：

Zheng, Hao ^{[1
]}

Dai, Tao ^{[1
]}

Zhou, Binquan ^{[1
]}

Zhu, Junhui ^{[1
]}

Huang, He ^{[1
]}

Wang, Min ^{[1
]}

Fu, Guosheng ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Med, Sir Run Run Shaw Hosp, Dept Cardiol,Biomed Res Therapy Ctr, Hangzhou 310016, Zhejiang, Peoples R China

来源：

ATHEROSCLEROSIS | 2008年 / 201卷 / 01期

关键词：

Endothelial progenitor cells; Stromal cell-derived factor-1 alpha; Apoptosis; Akt; eNOS; MAP kinases;

D O I：

10.1016/j.atherosclerosis.2008.02.011

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

Recent studies have demonstrated that stromal cell-derived factor-1 alpha (SDF-1 alpha)/CXCR4 interaction regulates multiple cell signal pathways and a variety of cellular functions such as cell migration, proliferation, survival and angiogenesis. In present study, we aimed to determine the effect of SDF-1 alpha on endothelial progenitor cells (EPCs) apoptosis induced by serum deprivation and the implication of phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs) signaling in this effect. EPCs were isolated and characterized. SDF-1 alpha decreased EPCs apoptosis induced by serum deprivation in a dose-dependent manner and the inhibitory effect was CXCR4 dependent as confirmed by the total abolishment by AMD3100, a CXCR4-specific peptide antagonist. SDF-1 alpha treatment also significant decreased caspase-3 expression and activity. The inhibitory effect of SDF-1 alpha on EPCs apoptosis was nearly completely abolished by PI3K inhibitors (either Wortmannin or LY294002) and partially abolished by NOS inhibitor, N-G-nitro-arginine methyl ester, whereas inhibitors of MAPKs had no significant effect on this inhibitory effect. The treatment of EPCs with SDF-1 alpha resulted in time-dependent Akt, eNOS, extracellular-regulated kinase (ERK 1/2), p38 MAPK and c-Jun N-terminal kinase (JNK) phosphorylations. These findings suggest that PI3K/Akt/eNOS activation, but not MAPKs activation, is required for the inhibitory effect of SDF-1 alpha on EPCs apoptosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

引用

页码：36 / 42

页数：7

共 26 条

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