scholarly journals Phosphoproteomic Analysis of Rat Neutrophils Shows the Effect of Intestinal Ischemia/Reperfusion and Preconditioning on Kinases and Phosphatases

2020 ◽  
Vol 21 (16) ◽  
pp. 5799
Author(s):  
Muhammad Tahir ◽  
Samina Arshid ◽  
Belchor Fontes ◽  
Mariana S. Castro ◽  
Simone Sidoli ◽  
...  
Keyword(s):  
Protective Effect ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Morbidity ◽  
Ischemia And Reperfusion ◽  
Cellular Functions ◽  
Regulation Mechanisms ◽  
And Migration ◽  
Intestinal Ischemia Reperfusion

Intestinal ischemia reperfusion injury (iIRI) is a severe clinical condition presenting high morbidity and mortality worldwide. Some of the systemic consequences of IRI can be prevented by applying ischemic preconditioning (IPC), a series of short ischemia/reperfusion events preceding the major ischemia. Although neutrophils are key players in the pathophysiology of ischemic injuries, neither the dysregulation presented by these cells in iIRI nor the protective effect of iIPC have their regulation mechanisms fully understood. Protein phosphorylation, as well as the regulation of the respective phosphatases and kinases are responsible for regulating a large number of cellular functions in the inflammatory response. Moreover, in previous work we found hydrolases and transferases to be modulated in iIR and iIPC, suggesting the possible involvement of phosphatases and kinases in the process. Therefore, in the present study, we analyzed the phosphoproteome of neutrophils from rats submitted to mesenteric ischemia and reperfusion, either submitted or not to IPC, compared to quiescent controls and sham laparotomy. Proteomic analysis was performed by multi-step enrichment of phosphopeptides, isobaric labeling, and LC-MS/MS analysis. Bioinformatics was used to determine phosphosite and phosphopeptide abundance and clustering, as well as kinases and phosphatases sites and domains. We found that most of the phosphorylation-regulated proteins are involved in apoptosis and migration, and most of the regulatory kinases belong to CAMK and CMGC families. An interesting finding revealed groups of proteins that are modulated by iIR, but such modulation can be prevented by iIPC. Among the regulated proteins related to the iIPC protective effect, Vamp8 and Inpp5d/Ship are discussed as possible candidates for control of the iIR damage.

Mucosal arachidonate metabolism and intestinal ischemia-reperfusion injury

1989 ◽  
Vol 257 (2) ◽  
pp. G299-G307 ◽  
Author(s):  
M. J. Mangino ◽  
C. B. Anderson ◽  
M. K. Murphy ◽  
E. Brunt ◽  
J. Turk
Keyword(s):  
Blood Flow ◽  
Reperfusion Injury ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Leukotriene B4 ◽  
Time Dependent ◽  
Ischemia And Reperfusion ◽  
Synthesis Inhibitor ◽  
Intestinal Ischemia Reperfusion

Mucosal arachidonic acid metabolism was examined after 3 h of ischemia and 1 h of reperfusion in isolated ileal segments in the dog. The cyclooxygenase products thromboxane B2, 6-ketoprostaglandin F1 alpha, and prostaglandin E2 increased by 365%, 97%, and 158%, respectively, after ischemia and reperfusion but were not altered after 3 h of ischemia alone. The potent chemotactic lipoxygenase product leukotriene B4 (LTB4) increased by 687% after ischemia and reperfusion and was not affected by ischemia without reperfusion. In addition, tissue production of the thiol ether leukotrienes (LTC4, LTD4, and LTE4) increased threefold after ischemia and reperfusion. Quantitation of regionally isomeric hydroxy acids produced from arachidonate revealed a 300% increase in 12-hydroxyeicosatetraenoate (12-HETE) after intestinal ischemia and reperfusion without a change in other isomers (15-HETE and 5-HETE). Stereochemical analysis of 12-HETE demonstrated exclusive synthesis of the S-enantiomer. A significant and time-dependent decrease in intestinal blood flow also occurred during reperfusion. Administration of the dual cyclooxygenase-lipoxygenase synthesis inhibitor BW755C (1 mg/kg ia) did not alter time-dependent decreases in blood flow and failed to inhibit eicosanoid synthesis. Histologic examinations of intestinal samples revealed significant mucosal damage associated with ischemia alone and ischemia after reperfusion. This study indicates that intestinal ischemia-reperfusion injury is associated with dramatic alterations in mucosal production of vasoactive eicosanoids and with changes in blood flow that occur during reperfusion but not during ischemia alone. These events may be involved in the pathology characteristic of this injury.

scholarly journals Protective effect of allopurinol against intestinal ischemia-reperfusion injury

2015 ◽  
Vol 23 (11) ◽  
pp. 1796
Author(s):  
Xiao-Juan Dai ◽  
Tao Yang ◽  
Mei-Xia Xu ◽  
Hao-Hao Cao ◽  
Xiao-Xia Zhang ◽  
...  
Keyword(s):  
Protective Effect ◽  
Reperfusion Injury ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Intestinal Ischemia Reperfusion

scholarly journals Protective effects of berberine on intestinal ischemia and reperfusion injury in rats

2017 ◽  
Vol 69 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Tanzhou Chen ◽  
Bin Lv
Keyword(s):  
Reperfusion Injury ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Immunoglobulin A ◽  
Male Rats ◽  
Ischemia And Reperfusion ◽  
Protective Effects ◽  
Ischemia And Reperfusion Injury ◽  
Intestinal Ischemia Reperfusion

This study aims to investigate the potential protective effects of berberine on ischemia and reperfusion (IR) injury in rats. Thirty male rats were randomly divided into three experimental groups as follows: the sham group, the IR group and the berberine+IR group. Intestinal ischemia-reperfusion was performed by occlusion of the superior mesenteric artery for 30 min, followed by 2-h reperfusion. The berberine+IR group of rats were administered 200 mg/kg of berberine once a day for 7 days before laparotomy. Compared with the IR group, rats pretreated with berberine prior to IR had significantly reduced intestinal ischemia/reperfusion injury and a significant reduction in Chiu?s score (p<0.05). The level of malondialdehyde and myeloperoxidase in the berberine+IR group was significantly decreased compared with the IR group (p<0.001). Superoxide dismutase activity in the berberine+IR group was significantly higher than in the IR group (p<0.001). Compared with the IR group, diamine oxidase was markedly decreased in the berberine+IR group (p<0.01). The level of secretory immunoglobulin A in the berberine+IR group was significantly increased when compared to the IR group (p<0.001). Our results suggest that berberine can protect from intestinal IR injury and that it can be beneficial in treating conditions associated with intestinal IR injury.

scholarly journals Dexmedetomidine Ameliorates Lung Injury Induced by Intestinal Ischemia/Reperfusion by Upregulating Cannabinoid Receptor 2, Followed by the Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Meng Chen ◽  
Xue-Tao Yan ◽  
Li Ye ◽  
Jun-Jiao Tang ◽  
Zong-Ze Zhang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Protective Effect ◽  
Receptor Antagonist ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Akt Pathway ◽  
High Morbidity ◽  
Protective Effects ◽  
Sod Activity ◽  
Intestinal Ischemia Reperfusion

Intestinal ischemia/reperfusion (I/R) is a clinical emergency, which often causes lung injury with high morbidity and mortality. Although dexmedetomidine has been identified to have a protective effect on lung injury caused by intestinal I/R, its specific mechanism is still elucidated. In recent years, the cannabinoid (CB2) receptor pathway has been found to be involved in I/R injury of some organs. In the current study, we investigated whether the CB2 receptor pathway contributes to the protective effect of dexmedetomidine on the intestinal I/R-induced lung injury in rats. Dexmedetomidine treatment upregulated the expression of CB2 receptor and suppressed the I/R-induced increases in lung injury scores, inflammatory cell infiltration, lung wet/dry ratio, MPO activity, MDA level, inflammatory cytokines, and caspase-3 expression while augmenting SOD activity and Bcl-2 expression, indicating attenuation of lung injury. Dexmedetomidine treatment also increased the expression of Akt. The protective effects of dexmedetomidine treatment were reversed by the CB2 receptor antagonist AM630 or the PI3K inhibitor wortmannin. And the CB2 receptor antagonist AM630 also downregulated the expression of Akt. Thus, our findings suggest that treatment with dexmedetomidine provides a protective role against lung injury caused by intestinal I/R in rats, possibly due to the upregulation of the CB2 receptor, followed by the activation of the PI3K/Akt pathway.

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