PMID- 16699462
OWN - NLM
STAT- MEDLINE
DCOM- 20060626
LR  - 20091119
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 81
IP  - 9
DP  - 2006 May 15
TI  - JNK (c-Jun NH2 terminal kinase) and p38 during ischemia reperfusion injury in the 
      small intestine.
PG  - 1325-30
AB  - BACKGROUND: In small intestinal ischemia reperfusion injury, we investigated the 
      pathophysiological role of c-Jun NH2 terminal kinase (JNK) and p38 in order to 
      determine whether the dual inhibition of JNK and p38 was beneficial. METHODS: 
      Ischemia reperfusion injury was induced by clamping the superior mesenteric 
      artery for 30 min in Wistar male rats. The inhibition of JNK and p38 was achieved 
      with LL-Z1640-2 as a novel JNK and p38 dual inhibitor in vivo. Between the 
      non-treatment group (Control group) and the LL-Z1640-2 treatment group (LL-Z 
      group), the following findings were compared; histological damage by hematoxylin 
      and eosin (H. E.) staining, JNK and p38 activation by a kinase assay, the 
      localization of apoptosis using the terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) method, the localization of 
      activated JNK and activated p38 based on immunohistochemistry. RESULTS: The 
      activation of JNK and p38 increased remarkably after reperfusion according to a 
      kinase assay. In immunohistochemistry for activated JNK and activated p38, a 
      remarkable degree of positive staining was revealed in the nucleus of the 
      detached epithelial cells from the tip of villi after reperfusion. In addition, 
      many TUNEL positive cells were observed in the detached epithelial cells where 
      JNK and p38 were activated. Pretreatment of LL-Z1640-2 inhibited the activation 
      of JNK and p38, and also significantly improved the histological damage. 
      CONCLUSIONS: These results suggest that JNK and p38 both play a key role during 
      small intestinal ischemia reperfusion injury through a proapoptotic action on the 
      tip of villi.
FAU - Murayama, Takaya
AU  - Murayama T
AD  - Department of Surgery, Keio University School of Medicine, and Department of 
      Pathology, Saiseikai Central Hospital, Tokyo, Japan.
FAU - Tanabe, Minoru
AU  - Tanabe M
FAU - Matsuda, Satoshi
AU  - Matsuda S
FAU - Shimazu, Motohide
AU  - Shimazu M
FAU - Kamei, Shusaku
AU  - Kamei S
FAU - Wakabayashi, Go
AU  - Wakabayashi G
FAU - Kawachi, Shigeyuki
AU  - Kawachi S
FAU - Matsumoto, Kenji
AU  - Matsumoto K
FAU - Yamazaki, Kazuto
AU  - Yamazaki K
FAU - Matsumoto, Koshi
AU  - Matsumoto K
FAU - Koyasu, Shigeo
AU  - Koyasu S
FAU - Kitajima, Masaki
AU  - Kitajima M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Enzyme Activation
MH  - In Situ Nick-End Labeling
MH  - Intestinal Mucosa/enzymology/pathology
MH  - Intestine, Small/*enzymology/pathology/physiopathology
MH  - Male
MH  - Microvilli/enzymology/pathology
MH  - Mitogen-Activated Protein Kinase 8/*metabolism
MH  - Models, Animal
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Wistar
MH  - Reperfusion Injury/*enzymology
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
EDAT- 2006/05/16 09:00
MHDA- 2006/06/27 09:00
CRDT- 2006/05/16 09:00
PHST- 2006/05/16 09:00 [pubmed]
PHST- 2006/06/27 09:00 [medline]
PHST- 2006/05/16 09:00 [entrez]
AID - 00007890-200605150-00017 [pii]
AID - 10.1097/01.tp.0000209167.48030.6b [doi]
PST - ppublish
SO  - Transplantation. 2006 May 15;81(9):1325-30. doi: 
      10.1097/01.tp.0000209167.48030.6b.