TY - JOUR
T1 - Inhibitory effects of purpurogallin on the endothelial protein C receptor shedding in vitro and in vivo
AU - Ku, Sae Kwang
AU - Lee, In Chul
AU - Bae, Jong Sup
PY - 2013/10
Y1 - 2013/10
N2 - Endothelial cell protein C receptor (EPCR) plays important roles in the regulation of blood coagulation and inflammation. Activity of EPCR is markedly changed by ectodomain cleavage and released as soluble protein (sEPCR). EPCR can be shed from the cell surface, and this is mediated by tumor necrosis factor-α converting enzyme (TACE). Purpurogallin (PPG) plays an important role in inhibiting glutathione S-transferase and xanthine oxidase as well as effective in the cell protection of several cell types. Here, we investigated the effects of PPG on phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and on cecal ligation and puncture (CLP)-mediated EPCR shedding and underlying mechanisms. Human umbilical vein endothelial cells pretreated with PPG (0, 5, 10, 20 or 50 μg/mL) for 6 h and exposed to PMA (1 μM) for 1 h, and CLP-operated mice were administrated with PPG. Data showed that treatment with PPG resulted in potent inhibition of PMA, TNF-α, IL-1β, and CLP-induced EPCR shedding by suppression of TACE expression. In addition, PPG reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases 1/2, and c-Jun N-terminal kinase. These results suggest the potential for use of PPG as an anti-sEPCR shedding reagent against PMA and CLP-mediated EPCR shedding.
AB - Endothelial cell protein C receptor (EPCR) plays important roles in the regulation of blood coagulation and inflammation. Activity of EPCR is markedly changed by ectodomain cleavage and released as soluble protein (sEPCR). EPCR can be shed from the cell surface, and this is mediated by tumor necrosis factor-α converting enzyme (TACE). Purpurogallin (PPG) plays an important role in inhibiting glutathione S-transferase and xanthine oxidase as well as effective in the cell protection of several cell types. Here, we investigated the effects of PPG on phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and on cecal ligation and puncture (CLP)-mediated EPCR shedding and underlying mechanisms. Human umbilical vein endothelial cells pretreated with PPG (0, 5, 10, 20 or 50 μg/mL) for 6 h and exposed to PMA (1 μM) for 1 h, and CLP-operated mice were administrated with PPG. Data showed that treatment with PPG resulted in potent inhibition of PMA, TNF-α, IL-1β, and CLP-induced EPCR shedding by suppression of TACE expression. In addition, PPG reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases 1/2, and c-Jun N-terminal kinase. These results suggest the potential for use of PPG as an anti-sEPCR shedding reagent against PMA and CLP-mediated EPCR shedding.
KW - cecal ligation and puncture
KW - endothelial cell protein C receptor
KW - phorbol-12-myristate 13-acetate
KW - purpurogallin
KW - shedding
UR - http://www.scopus.com/inward/record.url?scp=84886742400&partnerID=8YFLogxK
U2 - 10.1007/s13765-013-3169-7
DO - 10.1007/s13765-013-3169-7
M3 - Article
AN - SCOPUS:84886742400
SN - 1738-2203
VL - 56
SP - 519
EP - 524
JO - Journal of the Korean Society for Applied Biological Chemistry
JF - Journal of the Korean Society for Applied Biological Chemistry
IS - 5
ER -