Salvianolic acid B protects human endothelial cells from oxidative stress damage: A possible protective role of glucose-regulated protein 78 induction

Hong Li Wu, Yu Hua Li, Yan Hua Lin, Rui Wang, Ying Bo Li, Lu Tie, Qian Liu Song, De An Guo, He Ming Yu, Xue Jun Li

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

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 2α (eIF2α) 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-eIF2α-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.

Original languageEnglish
Pages (from-to)148-158
Number of pages11
JournalCardiovascular Research
Volume81
Issue number1
DOIs
StatePublished - 1 Jan 2009

Keywords

  • Endoplasmic reticulum stress
  • Endothelial cell
  • GRP78
  • Oxidative stress
  • Salvianolic acid B

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