Effect of endoplasmic reticulum stress on uremic serum-induced endothelial cell dysfunction

Wei ZENG, Zhi-feng LUO, Wei QI, Yan-hong GUO, Qi PANG, Jun ZHANG, Zong-qian WANG, Jiao MU, Bing FENG
2011 Medical Journal of Chinese People's Liberation Army  
Objective To investigate the effect of endoplasmic reticulum stress in uremic serum-induced endothelial cell dysfunction.Methods Human umbilical vein endothelial cells(hUVECs) were cultured in growth medium with the addition of uremic serum collected from uremic patients in different concentrations,or normal serum collected from normal adults for 24h.The cell viability was then tested by MTT assay and the cell cycle was analyzed by flow cytometry(FCM).Hoechst33342 assay was used to analyze the
more » ... sed to analyze the apoptotic effect of uremic serum on hUVECs.The cellular mRNA expressions of monocyte chemotactic protein-1(MCP-1) and glucose-regulated protein 78(GRP78) were measured by real-time fluorescence PCR.Results Co-cultured with lower concentrations of uremic serum( < 10%),the proliferation and percentage of S stage of cell cycle in hUVECs increased gradually and significantly.In contrast,the proliferation of hUVECs decreased gradually and the apoptosis of hUVECs increased when cultured with higher concentrations( > 10%) of uremic serum.Expressions of GRP78 and MCP-1 mRNA increased significantly in 10% uremic serum than in normal serum(P < 0.05).However,induction of expressions of GRP78 and MCP-1 mRNA by uremic serum could be inhibited significantly by the chemical chaperone 4-phenylbutyric acid(4-PBA)(P < 0.05).Furthermore,cell viability and the percentage of S stage of hUVECs were decreased(P < 0.05).Conclusion Endoplasmic reticulum stress plays a critical role in uremic serum-induced endothelial cell dysfunction.
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