Etomidate Alleviates Ischemia-Anoxia Reperfusion Injury in Intestinal Epithelial Cells by Inhibiting the Activation of traf6-Regulated NF-KB Signaling

2022 ◽  
Vol 12 (5) ◽  
pp. 1015-1021
Gen Lin ◽  
Ruichun Long ◽  
Xiaoqing Yang ◽  
Songsong Mao ◽  
Hongying Li

Objective: The present study aimed to investigate the role of etomidate in intestinal cell ischemia and hypoxia-reperfusion injury and potential mechanisms. Method: In this study, we establish the intestinal epithelial cells ischemia-reperfusion model in vitro. CCK8 was used to detect cell viability and flow cytometry assay was used to detect apoptosis levels of treated OGD/R model cells. ELISA measured the expression level of oxidative stress factors and inflammatory factors. Furthermore, western blot assay was used to detect the expression the apoptosis-related factors and TNFR-associated factors in treated OGD/R model cells. Result: Etomidate does not affect the activity of intestinal epithelial cells, and can protect intestinal epithelial cells to reduce ischemiareperfusion injury, and the expression of inflammatory factors and oxidative stress in cells with mild intestinal epithelial ischemia-reperfusion injury. Etomidate alleviates apoptosis of intestinal epithelial ischemia-reperfusion injury cells. Etomidate inhibits the activation of traf6-mediated NF-κB signal during ischemia-anoxia reperfusion of intestinal epithelial cells. Conclusion: Taken together, our study demonstrated that etomidate attenuates inflammatory response and apoptosis in intestinal epithelial cells during ischemic hypoxia-reperfusion injury and inhibits activation of NF-κB signaling regulated by TRAF6.

2021 ◽  
Atsushi Senda ◽  
Mitsuaki Kojima ◽  
Arisa Watanabe ◽  
Tetsuyuki Kobayashi ◽  
Keita Nakatsutsumi ◽  

Abstract Intestinal ischemia-reperfusion injury leads to multiple organ injuries via gut-derived mediators following severe injury. Growing evidence suggests that exosomes secreted from intestinal epithelial cells are heavily involved in the development of systemic inflammation, but a full elucidation of its pathology remains to be completed. To produce an integrated understanding of its pathology, this study aimed to reveal the changes in exosome content after ischemic stimulation. Our result showed (1) the proteins involved in inflammation by catalyzing RNAs were upregulated, (2) hsa-miR-21-5p, hsa-miR-23a-3p, and hsa-miR-30d-5p levels were increased while hsa-miR-124-3p level was decreased, (3) the increase in unsaturated lysophosphatidylcholines levels. These results together with those of previous studies, suggest that lysophosphatidylcholines may activate the NK-κB pathway. The proteins and microRNAs jointly act to disrupt negative feedback, thereby increasing inflammation. Thus, our results clarify part of the mechanism of multi-organ failure after intestinal ischemic recanalization, thereby providing a new target for treatment.

2006 ◽  
Vol 290 (6) ◽  
pp. C1469-C1476 ◽  
Jun Song ◽  
Jing Li ◽  
Andrew Lulla ◽  
B. Mark Evers ◽  
Dai H. Chung

Protein kinase D (PKD) is a novel protein serine kinase that has recently been implicated in diverse cellular functions, including apoptosis and cell proliferation. The purpose of our present study was 1) to define the activation of PKD in intestinal epithelial cells treated with H2O2, an agent that induces oxidative stress, and 2) to delineate the upstream signaling mechanisms mediating the activation of PKD. We found that the activation of PKD is induced by H2O2 in both a dose- and time-dependent fashion. PKD phosphorylation was attenuated by rottlerin, a selective PKC-δ inhibitor, and by small interfering RNA (siRNA) directed against PKC-δ, suggesting the regulation of PKD activity by upstream PKC-δ. Activation of PKD was also blocked by a Rho kinase (ROK)-specific inhibitor, Y-27632, as well as by C3, a Rho protein inhibitor, demonstrating that the Rho/ROK pathway also mediates PKD activity in intestinal cells. In addition, H2O2-induced PKC-δ phosphorylation was inhibited by C3 treatment, further suggesting that PKC-δ is downstream of Rho/ROK. Interestingly, H2O2-induced intestinal cell apoptosis was enhanced by PKD siRNA. Together, these results clearly demonstrate that oxidative stress induces PKD activation in intestinal epithelial cells and that this activation is regulated by upstream PKC-δ and Rho/ROK pathways. Importantly, our findings suggest that PKD activation protects intestinal epithelial cells from oxidative stress-induced apoptosis. These findings have potential clinical implications for intestinal injury associated with oxidative stress (e.g., necrotizing enterocolitis in infants).

2010 ◽  
Vol 17 (12) ◽  
pp. 989-995 ◽  
Taiji Hayashi ◽  
Marco Antonio De Velasco ◽  
Yoshitaka Saitou ◽  
Kazuhiro Nose ◽  
Tsukasa Nishioka ◽  

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