title: Suppressive Effects of Pelargonidin on Endothelial Protein C Receptor Shedding via the Inhibition of TACE Activity and MAP Kinases.
abstract: Beyond its role in the activation of protein C, the endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-[Formula: see text] converting enzyme (TACE). Pelargonidin is a well-known red pigment found in plants, and has been reported to have important biological activities that are potentially beneficial to human health. However, little is known about the effects of pelargonidin on EPCR shedding. We investigated this issue by monitoring the effects of pelargonidin on phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-[Formula: see text]-, interleukin (IL)-1β-, and cecal ligation and puncture (CLP)-mediated EPCR shedding and by investigating the underlying mechanism of pelargonidin action. Data demonstrate that pelargonidin induced potent inhibition of PMA-, TNF-[Formula: see text]-, IL-1β-, and CLP-induced EPCR shedding by inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs) such as p38, janus kinase (JNK), and extracellular signal-regulated kinase (ERK) 1/2. Pelargonidin also inhibited the expression and activity of PMA-induced TACE in endothelial cells. These results demonstrate the potential of pelargonidin as an anti-EPCR shedding reagent against PMA- and CLP-mediated EPCR shedding.
authors.affiliation: 1 College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Kang
authors.affiliation: 1 College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Taeho
authors.initials: T
authors.lastname: Lee
authors.affiliation: 1 College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000072198:ADAM17 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000872:Anthocyanins / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D000074283:Endothelial Protein C Receptor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; C478370:PROCR protein, human; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C066957:pelargonidin; D048049:Extracellular Signal-Regulated MAP Kinases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; D013755:Tetradecanoylphorbol Acetate
keywords: CLP; EPCR Shedding; Pelargonidin; Vascular Inflammation