PMID- 23774263
OWN - NLM
STAT- MEDLINE
DCOM- 20140328
LR  - 20231213
IS  - 1873-6351 (Electronic)
IS  - 0278-6915 (Linking)
VI  - 59
DP  - 2013 Sep
TI  - Rosmarinic acid down-regulates endothelial protein C receptor shedding in vitro 
      and in vivo.
PG  - 311-5
LID - S0278-6915(13)00369-4 [pii]
LID - 10.1016/j.fct.2013.06.003 [doi]
AB  - The endothelial protein C receptor (EPCR) plays pivotal roles in coagulation and 
      inflammation, however, its activity is markedly changed by ectodomain cleavage 
      and release as the soluble protein (sEPCR). According to previous studies, there 
      are approximately 100ng/ml sEPCR in human plasma and the levels increase in 
      inflammatory diseases. EPCR can be shed from the cell surface, and this is 
      mediated by tumor necrosis factor-alpha converting enzyme (TACE). We recently 
      reported on the anti-inflammatory and barrier protective activities of rosmarinic 
      acid (RA), an important component of the leaves of Perilla frutescens. However, 
      little is known about the effects of RA on EPCR shedding. Here, we investigated 
      this issue by monitoring the effects of RA on phorbol-12-myristate 13-acetate 
      (PMA), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta, and on cecal 
      ligation and puncture (CLP)-mediated EPCR shedding and underlying mechanisms. 
      Data showed that treatment with RA resulted in potent inhibition of PMA, TNF-alpha, 
      IL-induced EPCR shedding by suppression of TACE expression. In addition, RA 
      reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases 
      (ERK) 1/2, and c-Jun N-terminal kinase (JNK). These results suggest the potential 
      for use of RA as an anti-sEPCR shedding reagent against PMA, TNF-alpha, IL-1beta and 
      CLP-mediated EPCR shedding.
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 - Yang, Eun-Ju
AU  - Yang EJ
FAU - Song, Kyung-Sik
AU  - Song KS
FAU - Bae, Jong-Sup
AU  - Bae JS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130614
PL  - England
TA  - Food Chem Toxicol
JT  - Food and chemical toxicology : an international journal published for the British 
      Industrial Biological Research Association
JID - 8207483
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antigens, CD)
RN  - 0 (Cinnamates)
RN  - 0 (Depsides)
RN  - 0 (Endothelial Protein C Receptor)
RN  - 0 (PROCR protein, human)
RN  - 0 (Peptide Fragments)
RN  - 0 (Procr protein, mouse)
RN  - 0 (Receptors, Cell Surface)
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)
SB  - IM
MH  - ADAM Proteins/antagonists & inhibitors/metabolism
MH  - ADAM17 Protein
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology/*therapeutic use
MH  - Antigens, CD/chemistry/metabolism
MH  - Cells, Cultured
MH  - Cinnamates/pharmacology/*therapeutic use
MH  - Depsides/pharmacology/*therapeutic use
MH  - *Disease Models, Animal
MH  - Down-Regulation/*drug effects
MH  - Endothelial Protein C Receptor
MH  - Endothelium, Vascular/cytology/*drug effects/immunology/metabolism
MH  - Human Umbilical Vein Endothelial Cells/cytology/drug 
      effects/immunology/metabolism
MH  - Humans
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Peptide Fragments/blood/chemistry/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Processing, Post-Translational/drug effects
MH  - Proteolysis
MH  - Receptors, Cell Surface/blood/chemistry/*metabolism
MH  - Sepsis/blood/*drug therapy/immunology/metabolism
MH  - Solubility
MH  - Rosmarinic Acid
OTO - NOTNLM
OT  - CLP
OT  - EPCR
OT  - PMA
OT  - Rosmarinic acid
OT  - Shedding
EDAT- 2013/06/19 06:00
MHDA- 2014/03/29 06:00
CRDT- 2013/06/19 06:00
PHST- 2013/01/20 00:00 [received]
PHST- 2013/05/30 00:00 [revised]
PHST- 2013/06/06 00:00 [accepted]
PHST- 2013/06/19 06:00 [entrez]
PHST- 2013/06/19 06:00 [pubmed]
PHST- 2014/03/29 06:00 [medline]
AID - S0278-6915(13)00369-4 [pii]
AID - 10.1016/j.fct.2013.06.003 [doi]
PST - ppublish
SO  - Food Chem Toxicol. 2013 Sep;59:311-5. doi: 10.1016/j.fct.2013.06.003. Epub 2013 
      Jun 14.