Influence of pituitary adenylate cyclase-activating polypeptide on the activation of mitogen activated protein kinases following small bowel cold preservation.

ABSTRACT

Cold preservation prior to small bowel transplantation can moderate tissue oxidative injury. This stress triggers several intracellular pathways via mitogen activated protein (MAP) kinases. MAP kinases include the extracellular signal related kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAP kinase. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays a central role in intestinal physiology. We sought to investigate the effect of PACAP on the activation of MAP kinases during cold preservation of the small bowel. Total orthotopic intestinal autotransplantation was performed on 40 Wistar rats. Perfused grafts were stored in University of Wisconsin (UW) solution for 1 (GI), 2 (GII), 3 (GIII), or 6 hours (GIV) without or with 30 PACAP, namely 1 (GV), 2 (GVI), 3 (GVII), or 6 hours (GVIII). After 3 hours of reperfusion in all groups, the activation of MAP kinases were measured using immunocytochemistry of small bowel tissue. Among the UW preserved grafts (GI-GIV), phosphorylated ERK1/2 level were decreased, while phosphorylated JNK1/2 and p38 MAP kinase activation were elevated compared with control levels. In GV-GVIII PACAP we observed enhanced phospho-ERK1/2 appearance with decreased JNK and p38 MAP kinase activity at the end of the reperfusion periods. We concluded that cold preservation decreased phosphorylated ERK1/2 levels and increased JNK1/2 and p38 MAP kinase activities, which meant that cold storage triggered apoptotic cell death. In contrast, PACAP treatment induced signalling pathways protective against oxidative injury by MAP kinases in bowel tissue.