PMID- 24769195
OWN - NLM
STAT- MEDLINE
DCOM- 20150105
LR  - 20181202
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 84
DP  - 2014 Jun
TI  - Exendin-4 inhibits endothelial protein C receptor shedding in vitro and in vivo.
PG  - 18-25
LID - S1043-6618(14)00045-0 [pii]
LID - 10.1016/j.phrs.2014.04.005 [doi]
AB  - Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, has been reported to 
      attenuate myocardial ischemia and reperfusion (I/R) injury, inflammatory and 
      oxidative responses. Increasing evidence has demonstrated that beyond its role in 
      activation of protein C, endothelial cell protein C receptor (EPCR) is involved 
      in vascular inflammation. EPCR activity is markedly decreased by ectodomain 
      cleavage and release as the soluble EPCR. EPCR can be shed from the cell surface, 
      which is mediated by tumor necrosis factor-alpha converting enzyme (TACE). However, 
      little is known about the effects of EX4 on EPCR shedding. Data from this study 
      showed that EX4 induced potent inhibition of phorbol-12-myristate 13-acetate 
      (PMA), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta-induced EPCR 
      shedding in human umbilical vein endothelial cells (HUVECs), and cecal ligation 
      and puncture (CLP)-induced EPCR shedding in mice. EX4 also inhibited expression 
      and activity of TACE induced by PMA in HUVECs. In addition, treatment with EX4 
      resulted in reduced PMA-stimulated phosphorylation of p38, extracellular 
      regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). These results 
      demonstrate the potential of EX4 as an anti-sEPCR shedding reagent against PMA 
      and CLP-mediated EPCR shedding.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Ku, Sae-Kwang
AU  - Ku SK
AD  - Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany 
      University, Gyeongsan 712-715, Republic of Korea.
FAU - Han, Min-Su
AU  - Han MS
AD  - Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu 
      Fatima Hospital, Daegu 701-724, Republic of Korea.
FAU - Park, Eun Ji
AU  - Park EJ
AD  - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, 
      Kyungpook National University, Daegu 702-701, Republic of Korea.
FAU - Na, Dong Hee
AU  - Na DH
AD  - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, 
      Kyungpook National University, Daegu 702-701, Republic of Korea.
FAU - Bae, Jong-Sup
AU  - Bae JS
AD  - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, 
      Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic 
      address: baejs@knu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140424
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Blood Coagulation Factors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Venoms)
RN  - 0 (activated protein C receptor)
RN  - 9P1872D4OL (Exenatide)
RN  - E0399OZS9N (Cyclic AMP)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Animals
MH  - Blood Coagulation Factors/*drug effects/metabolism
MH  - Cecum/injuries
MH  - Cyclic AMP/metabolism
MH  - Endothelial Cells/drug effects
MH  - Exenatide
MH  - Human Umbilical Vein Endothelial Cells/drug effects
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology
MH  - In Vitro Techniques
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Peptides/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Primary Cell Culture
MH  - Receptors, Cell Surface/*drug effects/metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Venoms/*pharmacology
OTO - NOTNLM
OT  - EPCR shedding
OT  - Exendin-4
OT  - Vascular inflammation
EDAT- 2014/04/29 06:00
MHDA- 2015/01/06 06:00
CRDT- 2014/04/29 06:00
PHST- 2014/03/03 00:00 [received]
PHST- 2014/04/14 00:00 [revised]
PHST- 2014/04/14 00:00 [accepted]
PHST- 2014/04/29 06:00 [entrez]
PHST- 2014/04/29 06:00 [pubmed]
PHST- 2015/01/06 06:00 [medline]
AID - S1043-6618(14)00045-0 [pii]
AID - 10.1016/j.phrs.2014.04.005 [doi]
PST - ppublish
SO  - Pharmacol Res. 2014 Jun;84:18-25. doi: 10.1016/j.phrs.2014.04.005. Epub 2014 Apr 
      24.