PMID- 23726966 OWN - NLM STAT- MEDLINE DCOM- 20140310 LR - 20171116 IS - 1879-2472 (Electronic) IS - 0049-3848 (Linking) VI - 132 IP - 1 DP - 2013 Jul TI - Down-regulation of endothelial protein C receptor shedding by persicarin and isorhamnetin-3-O-galactoside. PG - e58-63 LID - S0049-3848(13)00196-5 [pii] LID - 10.1016/j.thromres.2013.05.004 [doi] AB - Increasing evidence has shown that beyond its role in coagulation, endothelial protein C receptor (EPCR) plays an important role in the cytoprotective pathway. Previous reports have shown that EPCR can be shed from the cell surface, and that this is mediated by tumor necrosis factor-alpha converting enzyme (TACE) and that sEPCR levels are increased in patients with systemic inflammatory diseases. Persicarin and isorhamnetin-3-O-galactoside (I3G) are active compounds from Oenanthe javanica, which has been widely studied for its neuroprotective, antioxidant, and barrier protective activities. However, little is known of the effects of persicarin on EPCR shedding. Here, we investigated this issue by monitoring the effects of persicarin and I3G on phorbol-12-myristate 13-acetate (PMA) and on cecal ligation and puncture (CLP)-mediated EPCR shedding and underlying mechanisms. According to the results, persicarin and I3G induced potent inhibition of PMA and CLP-induced EPCR shedding by suppressing expression of TACE. In addition, persicarin and I3G reduced PMA-stimulated phosphorylation of p38MAPK, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). Given these results, persicarin and I3G could be used as a candidate therapeutic for treatment of severe vascular inflammatory diseases. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Ku, Sae-Kwang AU - Ku SK AD - Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea. FAU - Han, Min-Su AU - Han MS FAU - Bae, Jong-Sup AU - Bae JS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130530 PL - United States TA - Thromb Res JT - Thrombosis research JID - 0326377 RN - 0 (Antigens, CD) RN - 0 (Antioxidants) RN - 0 (Endothelial Protein C Receptor) RN - 0 (Flavones) RN - 0 (Galactosides) RN - 0 (PROCR protein, human) RN - 0 (Receptors, Cell Surface) RN - 0 (isorhamnetin-3-O-galactoside) RN - 0 (persicarin) RN - 56937-68-9 (phorbolol myristate acetate) RN - 9IKM0I5T1E (Quercetin) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) RN - EC 3.4.24.- (ADAM Proteins) RN - EC 3.4.24.86 (ADAM17 Protein) RN - EC 3.4.24.86 (ADAM17 protein, human) RN - EC 3.4.24.86 (Adam17 protein, mouse) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - ADAM Proteins/genetics MH - ADAM17 Protein MH - Animals MH - Antigens, CD/genetics/*metabolism MH - Antioxidants/isolation & purification/*pharmacology MH - Down-Regulation/*drug effects MH - Endothelial Protein C Receptor MH - Enzyme Activation/drug effects MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Flavones/isolation & purification/*pharmacology MH - Galactosides/isolation & purification/*pharmacology MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - MAP Kinase Kinase 4/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Oenanthe/chemistry MH - Quercetin/*analogs & derivatives/isolation & purification/pharmacology MH - Receptors, Cell Surface/genetics/*metabolism MH - Tetradecanoylphorbol Acetate/analogs & derivatives/pharmacology MH - p38 Mitogen-Activated Protein Kinases/metabolism OTO - NOTNLM OT - APC OT - EPCR OT - ERK OT - I3G OT - JNK OT - PAR-1 OT - PMA OT - TACE OT - activated protein C OT - c-Jun N-terminal kinase OT - endothelial protein C receptor OT - extracellular regulated kinase OT - isorhamnetin-3-O-galactoside OT - persicarin OT - phorbol-12-myristate 13-acetate OT - protease activated receptor-1 OT - sEPCR OT - shedding OT - soluble EPCR OT - tumor necrosis factor-alpha converting enzyme EDAT- 2013/06/04 06:00 MHDA- 2014/03/13 06:00 CRDT- 2013/06/04 06:00 PHST- 2013/01/22 00:00 [received] PHST- 2013/05/04 00:00 [revised] PHST- 2013/05/05 00:00 [accepted] PHST- 2013/06/04 06:00 [entrez] PHST- 2013/06/04 06:00 [pubmed] PHST- 2014/03/13 06:00 [medline] AID - S0049-3848(13)00196-5 [pii] AID - 10.1016/j.thromres.2013.05.004 [doi] PST - ppublish SO - Thromb Res. 2013 Jul;132(1):e58-63. doi: 10.1016/j.thromres.2013.05.004. Epub 2013 May 30.