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《Chinese Journal of Pathophysiology》 2017-09
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Ethanol extract of propolis protects vascular endothelial cells from oxidized low-density lipoprotein-induced apoptosis by inhibiting C/EBP homologous protein expression

XU Xiao-yan;SHAO Xia-yan;LIU Ying-xue;LI Dong-xuan;JIAO Peng;HAO Qi;TIAN Hua;YAO Shu-tong;College of Pharmacy,Taishan Medical University;College of Population and Family Planning,Taishan Medical University;College of Basic Medical Sciences,Taishan Medical University;Institute of Atherosclerosis,Taishan Medical University;  
AIM: To investigate the inhibitory effect of ethanol extract of propolis(EEP) on oxidized low-density lipoprotein( ox-LDL)-induced vascular endothelial cell apoptosis and the underlying molecular mechanisms. METHODS: Human umbilical vein endothelial cells( HUVECs) were pretreated with EEP(7. 5,15 and 30 mg/L) or 4-phenylbutyric acid( PBA,4 mmol/L) for 1 h and then treated with ox-LDL(100 mg/L) or tunicamycin( TM,4 mg/L) for 24 h. The cell viability and apoptosis were determined by MTT assay and Annexin V-FITC/PI double staining,respectively.The activities of lactic dehydrogenase( LDH) in the medium and caspase-3 in the HUVECs were measured. The protein and mRNA levels of C/EBP homologous protein( CHOP),a proapoptotic molecule under endoplasmic reticulum stress(ERS),and its downstream Bcl-2 were examined by Western blot and real-time PCR,respectively. RESULTS: Like PBA(an ERS inhibitor),EEP protected HUVECs from ox-LDL-induced injury in a dose-dependent manner,as assessed by the increased cell viability and the decreased LDH release,apoptotic rate and caspase-3 activation. The decrease in cell viability and the increases in LDH release,apoptotic rate and caspase-3 activation induced by TM,an ERS inducer,were also attenuated by EEP. Moreover,EEP suppressed ox-LDL-induced CHOP upregulation and Bcl-2 downregulation,and this effect was similar to that of PBA. Similarly,EEP significantly suppressed TM-induced CHOP upregulation both at the protein and mRNA levels. CONCLUSION: EEP may protect HUVECs from ox-LDL-induced apoptosis,and the mechanism is at least partially involved in suppressing CHOP-mediated ERS-associated apoptotic pathway.
【Key Words】: Ethanol extract of propolis C/EBP homologous protein Oxidized low-density lipoprotein Vascular endothelial cells Apoptosis
【Fund】: 国家自然科学基金资助项目(No.81570410;No.81202949);; 泰山医学院国家级大学生创新训练项目(No.201510439100;No.201510439126);; 山东省高等学校科技计划(No.J14LM52)
【CateGory Index】: R285.5
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