Department of Biochemistry, Zunyi Medical College, China.
Acta Biochim Biophys Sin (Shanghai). 2011 Oct;43(10):787-95. doi: 10.1093/abbs/gmr072. Epub 2011 Aug 22.
The cystine-cystine (CC) chemokine monocyte chemoattractant protein-1 (MCP-1) has been established playing a pathogenic role in the development of atherosclerosis due to its chemotactic ability of leading monocytes to locate to subendothelia. Recent studies have revealed more MCP-1 functions other than chemotaxis. Here we reported that various concentrations (0.1-100 ng/ml) of MCP-1 induced human umbilical vein endothelial cell (HUVEC) strain CRL-1730 apoptosis, caspase-9 activation, and a couple of mitochondrial alterations. Moreover, MCP-1 upregulated p53 expression of HUVECs and the p53-specific inhibitor pifithrin-α (PFTα) rescued the MCP-1-induced apoptosis of HUVECs. Furthermore, PKC (protein kinase C) activation or inhibition might also affect HUVECs apoptosis induced by MCP-1. These findings together demonstrate that MCP-1 exerts direct proapoptotic effects on HUVECs in vitro via a p53-dependent mitochondrial pathway.
半胱氨酸-半胱氨酸（CC）趋化因子单核细胞趋化蛋白-1（MCP-1）由于其趋化单核细胞定位到内皮下的能力，已被确定在动脉粥样硬化的发展中起致病作用。最近的研究揭示了 MCP-1 除趋化作用以外的更多功能。在这里，我们报告了不同浓度（0.1-100ng/ml）的 MCP-1 诱导人脐静脉内皮细胞（HUVEC）株 CRL-1730 凋亡、半胱天冬酶-9 激活和几种线粒体改变。此外，MCP-1 上调了 HUVECs 的 p53 表达，p53 特异性抑制剂 pifithrin-α（PFTα）挽救了 MCP-1 诱导的 HUVECs 凋亡。此外，蛋白激酶 C（PKC）的激活或抑制也可能影响 MCP-1 诱导的 HUVECs 凋亡。这些发现共同表明，MCP-1 通过依赖 p53 的线粒体途径在体外对 HUVECs 发挥直接促凋亡作用。
