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

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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. © The Author 2008.

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Wu, H. L., Li, Y. H., Lin, Y. H., Wang, R., Li, Y. B., Tie, L., … Li, X. J. (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. https://doi.org/10.1093/cvr/cvn262

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