title: Monocyte chemoattractant protein-1 induces endothelial cell apoptosis in vitro through a p53-dependent mitochondrial pathway.
abstract: 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.
authors.affiliation: Department of Biochemistry, Zunyi Medical College, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiping
authors.initials: X
authors.lastname: Liu
authors.forename: Huifeng
authors.initials: H
authors.lastname: Shang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Minzhang
authors.initials: M
authors.lastname: Qian
mesh_terms: D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation
chemical_list: D018932:Chemokine CCL2; D016159:Tumor Suppressor Protein p53