267 259

Cited 21 times in

PAR2 exerts local protection against acute pancreatitis via modulation of MAP kinase and MAP kinase phosphatase signaling.

Authors
 Wan Namkung  ;  Jae Seok Yoon  ;  Kyung Hwan Kim  ;  Min Goo Lee 
Citation
 AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, Vol.295(5) : 886-894, 2008 
Journal Title
 AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY 
ISSN
 0193-1857 
Issue Date
2008
MeSH
Animals ; Butadienes/pharmacology ; Ceruletide/toxicity ; Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Flavonoids/pharmacology ; Gene Expression Regulation/physiology ; MAP Kinase Kinase 4/antagonists & inhibitors ; MAP Kinase Kinase 4/metabolism ; Male ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Mitogen-Activated Protein Kinase Phosphatases/metabolism* ; Nitriles/pharmacology ; Pancreatitis/chemically induced ; Pancreatitis/metabolism* ; Rats ; Rats, Sprague-Dawley ; Receptor, PAR-2/genetics ; Receptor, PAR-2/metabolism* ; Signal Transduction/physiology*
Keywords
protease activated receptor ; caerulein ; pancreas
Abstract
During acute pancreatitis, protease-activated receptor 2 (PAR2) can be activated by interstitially released trypsin. In the mild form of pancreatitis, PAR2 activation exerts local protection against intrapancreatic damage, whereas, in the severe form of pancreatitis, PAR2 activation mediates some systemic complications. This study aimed to identify the molecular mechanisms of PAR2-mediated protective effects against intrapancreatic damage. A mild form of acute pancreatitis was induced by an intraperitoneal injection of caerulein (40 microg/kg) in rats. Effects of PAR2 activation on intrapancreatic damage and on mitogen-activated protein (MAP) kinase signaling were assessed. Caerulein treatment activated extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) within 15 min and maintained phosphorylation of ERK and JNK for 2 h in the rat pancreas. Although PAR2 activation by the pretreatment with PAR2-activating peptide (AP) itself increased ERK phosphorylation in rat pancreas, the same treatment remarkably decreased caerulein-induced activation of ERK and JNK principally by accelerating their dephosphorylation. Inhibition of ERK and JNK phosphorylation by the pretreatment with MAP/ERK kinase (MEK) or JNK inhibitors decreased caerulein-induced pancreatic damage that was similar to the effect induced by PAR2-AP. Notably, in caerulein-treated rats, PAR2-AP cotreatment highly increased the expression of a group of MAP kinase phosphatases (MKPs) that deactivate ERK and JNK. The above results imply that downregulation of MAP kinase signaling by MKP induction is a key mechanism involved in the protective effects of PAR2 activation on caerulein-induced intrapancreatic damage
Files in This Item:
T200803365.pdf Download
DOI
10.1152/ajpgi.00053.2008
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Yoon, Jae Seok(윤재석)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108200
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse