title: Down-regulation of endothelial protein C receptor shedding by persicarin and isorhamnetin-3-O-galactoside.
abstract: 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-α 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.
authors.affiliation: Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea.
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Min-Su
authors.initials: MS
authors.lastname: Han
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000072198:ADAM17 Protein; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D000074283:Endothelial Protein C Receptor; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047309:Flavones / Q000302:isolation & purification / Q000494:pharmacology*; D005697:Galactosides / Q000302:isolation & purification / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D031050:Oenanthe / Q000737:chemistry; D011794:Quercetin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000975:Antioxidants; D000074283:Endothelial Protein C Receptor; D047309:Flavones; D005697:Galactosides; C478370:PROCR protein, human; D011956:Receptors, Cell Surface; C581364:isorhamnetin-3-O-galactoside; C551071:persicarin; C016658:phorbolol myristate acetate; D011794:Quercetin; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse; D013755:Tetradecanoylphorbol Acetate
keywords: APC; EPCR; ERK; I3G; JNK; PAR-1; PMA; TACE; activated protein C; c-Jun N-terminal kinase; endothelial protein C receptor; extracellular regulated kinase; isorhamnetin-3-O-galactoside; persicarin; phorbol-12-myristate 13-acetate; protease activated receptor-1; sEPCR; shedding; soluble EPCR; tumor necrosis factor-α converting enzyme