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学科主题基础医学
Salvianolic acid B protects human endothelial cells from oxidative stress damage: a possible protective role of glucose-regulated protein 78 induction
Wu, Hong-Li1; Li, Yu-Hua1; Lin, Yan-Hua1; Wang, Rui1; Li, Ying-Bo1; Tie, Lu1; Song, Qian-Liu2; Guo, De-An3; Yu, He-Ming2; Li, Xue-Jun1
关键词Salvianolic Acid b Oxidative Stress Endothelial Cell Grp78 Endoplasmic Reticulum Stress
刊名CARDIOVASCULAR RESEARCH
2009
DOI10.1093/cvr/cvn262
81期:1页:148-158
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems
研究领域[WOS]Cardiovascular System & Cardiology
关键词[WOS]ENDOPLASMIC-RETICULUM STRESS ; RENAL EPITHELIAL-CELLS ; SMOOTH-MUSCLE-CELLS ; PLATELET-AGGREGATION ; ER CHAPERONE ; IN-VITRO ; GRP78 ; MILTIORRHIZA ; ANTIOXIDANT ; INJURY
英文摘要

Aims The purposes of the present study were to both evaluate the protective effects of Salvianolic acid B (Sal B) and to determine the possible molecular mechanisms by which Sal B protects endothelial cells from damage caused by oxidative stress.

Methods and results Pretreatment with Sal B markedly attenuated H2O2-induced viability loss, lactate dehydrogenase leakage and apoptosis in human umbilical vein endothelial cells (HUVECs). The mechanism of Sal B protection was studied using two-dimensional gel electrophoresis coupled with hybrid quadrupole time-of-flight mass spectrometry. Database searching implicated that glucose-regulated protein 78 (GRP78), a central regulator for endoplasmic reticulum (ER) stress, was up-regulated in Sal B-exposed HUVECs. GRP78 expression regulation was confirmed by western blot and RT-PCR (reverse transcription-polymerase chain reaction) analyses. Additionally, GRP94, which shares significant sequence homology with GRP78, was also up-regulated in Sal B-treated cells. Sal B caused pancreatic ER kinase (PKR)-like ER kinase (PERK) activation followed by the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha) and the expression of activating transcription factor 4 (ATF4). Knockdown of endogenous ATF4 expression partially repressed Sal B-induced GRP78 induction. Further investigation showed that ATF6 was also activated by Sal B. Knockdown of GRP78 by siRNA significantly reduced the protective effects of Sal B.

Conclusion The results suggest that Sal B induces the expression of GRP78 by activating ATF6 and the PERK-eIF2 alpha-ATF4 pathway. Furthermore, up-regulation of GRP78 by Sal B may play an important role in protecting human endothelial cells from oxidative stress-induced cellular damage.

语种英语
WOS记录号WOS:000261679100022
项目编号30171090 ; 30270528 ; 30572202 ; 30772571 ; 2004CB518902 ; B0700
资助机构National Natural Science Foundation of China ; 973 Program of the Ministry of Science and Technology in China ; Ministry of Education of China
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被引频次:47[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55308
专题北京大学基础医学院_药理学系
北京大学医学部管理机构_医学部
北京大学基础医学院
北京大学药学院_天然药物与仿生药物国家重点实验室
北京大学第二临床医学院_重症医学科
作者单位1.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pharmacol, Beijing 100083, Peoples R China
2.Natl Res Inst Family Planning, Beijing 100081, Peoples R China
3.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China
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Wu, Hong-Li,Li, Yu-Hua,Lin, Yan-Hua,et al. Salvianolic acid B protects human endothelial cells from oxidative stress damage: a possible protective role of glucose-regulated protein 78 induction[J]. CARDIOVASCULAR RESEARCH,2009,81(1):148-158.
APA Wu, Hong-Li.,Li, Yu-Hua.,Lin, Yan-Hua.,Wang, Rui.,Li, Ying-Bo.,...&Li, Xue-Jun.(2009).Salvianolic acid B protects human endothelial cells from oxidative stress damage: a possible protective role of glucose-regulated protein 78 induction.CARDIOVASCULAR RESEARCH,81(1),148-158.
MLA Wu, Hong-Li,et al."Salvianolic acid B protects human endothelial cells from oxidative stress damage: a possible protective role of glucose-regulated protein 78 induction".CARDIOVASCULAR RESEARCH 81.1(2009):148-158.
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