Saikosaponin C inhibits lipopolysaccharide-induced apoptosis by suppressing caspase-3 activation and subsequent degradation of focal adhesion kinase in human umbilical vein endothelial cells |
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Institution: | 1. Division of Cardiology, Yonsei University College of Medicine, Seoul, Republic of Korea;2. Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea;3. The Department of Medicine, Vanderbilt University, Nashville, TN, USA;4. Cardiovascular Research Center, Rhode Island Hospital and Brown Medical School, Providence, RI, USA;5. The Department of Applied Bioscience, College of Life Science, CHA University, Seoul, Republic of Korea |
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Abstract: | Bacterial lipopolysaccharide (LPS) is an important mediator of inflammation and a potent inducer of endothelial cell damage and apoptosis. In this study, we investigated the protective effects of saikosaponin C (SSc), one of the active ingredients produced by the traditional Chinese herb, Radix Bupleuri, against LPS-induced apoptosis in human umbilical endothelial cells (HUVECs). LPS triggered caspase-3 activation, which was found to be important in LPS-induced HUVEC apoptosis. Inhibition of caspase-3 also inhibited LPS-induced degradation of focal adhesion kinase (FAK), indicating that caspase-3 is important in LPS-mediated FAK degradation as well as in apoptosis in HUVECs. SSc significantly inhibited LPS-induced apoptotic cell death in HUVECs through the selective suppression of caspase-3. SSc was also shown to rescue LPS-induced FAK degradation and other cell adhesion signals. Furthermore, the protective effects of SSc against LPS-induced apoptosis were abolished upon pretreatment with a FAK inhibitor, highlighting the importance of FAK in SSc activity. Taken together, these results show that SSc efficiently inhibited LPS-induced apoptotic cell death via inhibition of caspase-3 activation and caspase-3-mediated-FAK degradation. Therefore, SSc represents a promising therapeutic candidate for the treatment of vascular endothelial cell injury and cellular dysfunction. |
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Keywords: | Lipopolysaccharide (LPS) Human umbilical vein endothelial cells (HUVECs) Endothelial cell apoptosis Saikosaponin C (SSc) Caspase-3 Focal adhesion kinase (FAK) |
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