Dataset Information

PKC? phosphorylates TRAF2 to protect against intestinal ischemia-reperfusion-induced injury.

ABSTRACT: Intestinal ischemia-reperfusion (I/R) is a common clinical problem that occurs during various clinical pathological processes. Excessive apoptosis has an indispensable role in intestinal I/R injury. Tumor necrosis factor receptor-associated factor 2 (TRAF2) and PKC? have an essential role in apoptosis. Here, we aimed to investigate the effects of PKC? and TRAF2 and to explore the correlation between PKC? and TRAF2 in intestinal I/R injury. Mice were subjected to intestinal I/R injury in vivo. In vitro experiments were conducted by treating Caco-2 cells with hypoxia/reoxygenation (H/R) stimulation to simulate intestinal I/R. Intestinal tissue samples and Caco-2 cells were examined using various approaches. Intestinal I/R induced the membrane translocation and phosphorylation of PKC?. Pretreatment with the PKC? activator phosphatidylcholine remarkably attenuated gut injury by suppressing apoptosis. H/R induced PKC? to combine with TRAF2, which was phosphorylated by PKC? at Ser55, but not at Ser11, under intestinal I/R or H/R conditions. In addition, TRAF2 Ser55 phosphorylation increased cell survival by inhibiting cell apoptosis in the H/R model. Mechanistically, TRAF2 Ser55 phosphorylation promoted NF-?B activation but suppressed c-Jun activation in Caco-2 cells under H/R conditions. The results of this study demonstrate that the PKC?/TRAF2 pathway represents a novel protective mechanism against intestinal I/R injury. Therefore, the PKC?/TRAF2 pathway is a novel target for potential treatments of intestinal I/R injury-related diseases.

SUBMITTER: Zhou W

PROVIDER: S-EPMC5550857 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

PKCζ phosphorylates TRAF2 to protect against intestinal ischemia-reperfusion-induced injury.

Zhou Wei W Yao Jihong J Wang Guangzhi G Chen Zhao Z Li Zhenlu Z Feng Dongcheng D Li Yang Y Qasim Wasim W Tan Wenzhi W Ning Shili S Tian Xiaofeng X

Cell death & disease 20170720 7

Intestinal ischemia-reperfusion (I/R) is a common clinical problem that occurs during various clinical pathological processes. Excessive apoptosis has an indispensable role in intestinal I/R injury. Tumor necrosis factor receptor-associated factor 2 (TRAF2) and PKCζ have an essential role in apoptosis. Here, we aimed to investigate the effects of PKCζ and TRAF2 and to explore the correlation between PKCζ and TRAF2 in intestinal I/R injury. Mice were subjected to intestinal I/R injury in vivo. In ...[more]

PMID: 28726782

Similar Datasets

Project description:Intestinal ischemia-reperfusion (I/R) injury is a devastating complication when the blood supply is reflowed in ischemic organs. Gastrin has critical function in regulating acid secretion, proliferation, and differentiation in the gastric mucosa. We aimed to determine whether gastrin has an effect on intestinal I/R damage. Intestinal I/R injury was induced by 60-min occlusion of the superior mesenteric artery followed by 60-min reperfusion, and the rats were induced to be hypergastrinemic by pretreated with omeprazole or directly injected with gastrin. Some hypergastrinemic rats were injected with cholecystokinin-2 (CCK-2) receptor antagonist prior to I/R operation. After the animal surgery, the intestine was collected for histological analysis. Isolated intestinal epithelial cells or crypts were harvested for RNA and protein analysis. CCK-2 receptor expression, intestinal mucosal damage, cell apoptosis, and apoptotic protein caspase-3 activity were measured. We found that high gastrin in serum significantly reduced intestinal hemorrhage, alleviated extensive epithelial disruption, decreased disintegration of lamina propria, downregulated myeloperoxidase activity, tumor necrosis factor-?, and caspase-3 activity, and lead to low mortality in response to I/R injury. On the contrary, CCK-2 receptor antagonist L365260 could markedly impair intestinal protection by gastrin on intestinal I/R. Severe edema of mucosal villi with severe intestinal crypt injury and numerous intestinal villi disintegrated were observed again in the hypergastrinemic rats with L365260. The survival in the hypergastrinemic rats after intestinal I/R injury was shortened by L365260. Finally, gastrin could remarkably upregulated intestinal CCK-2 receptor expression. Our data suggest that gastrin by omeprazole remarkably attenuated I/R induced intestinal injury by enhancing CCK-2 receptor expression and gastrin could be a potential mitigator for intestinal I/R damage in the clinical setting.

Dataset Information

PKC? phosphorylates TRAF2 to protect against intestinal ischemia-reperfusion-induced injury.

Publications

PKCζ phosphorylates TRAF2 to protect against intestinal ischemia-reperfusion-induced injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets