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JNK (c-Jun NH2 terminal kinase) and p38 during ischemia reperfusion injury in the small intestine.

AbstractBACKGROUND:
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.
AuthorsTakaya Murayama, Minoru Tanabe, Satoshi Matsuda, Motohide Shimazu, Shusaku Kamei, Go Wakabayashi, Shigeyuki Kawachi, Kenji Matsumoto, Kazuto Yamazaki, Koshi Matsumoto, Shigeo Koyasu, Masaki Kitajima
JournalTransplantation (Transplantation) Vol. 81 Issue 9 Pg. 1325-30 (May 15 2006) ISSN: 0041-1337 [Print] United States
PMID16699462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Mitogen-Activated Protein Kinase 8
  • p38 Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Apoptosis
  • Enzyme Activation
  • In Situ Nick-End Labeling
  • Intestinal Mucosa (enzymology, pathology)
  • Intestine, Small (enzymology, pathology, physiopathology)
  • Male
  • Microvilli (enzymology, pathology)
  • Mitogen-Activated Protein Kinase 8 (metabolism)
  • Models, Animal
  • Phosphorylation
  • Rats
  • Rats, Wistar
  • Reperfusion Injury (enzymology)
  • p38 Mitogen-Activated Protein Kinases (metabolism)

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