scholarly journals lncRNA AK054386 Functions as a ceRNA to Sequester miR-199 and Induce Sustained Endoplasmic Reticulum Stress in Hepatic Reperfusion Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Binghua Dai ◽  
Liang Qiao ◽  
Mingke Zhang ◽  
Lipeng Cheng ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Trauma ◽  
Protective Effects ◽  
Related Factors ◽  
Hepatic Ischemia ◽  
Cellular Models

Hepatic ischemia-reperfusion injury (IRI) is a very complex pathological process that is often associated with liver trauma and surgery, especially liver transplantation surgery. Although endoplasmic reticulum stress (ERS) plays a role in this process, the posttranscriptional regulators and the underlying mechanisms are still unclear. Here, we report that the lncRNA AK054386 was increased in hepatic IRI models. Furthermore, AK054386 can act as a “competing endogenous RNA (ceRNA)” and regulate ERS-related factors by binding and sequestering miR-199, which was shown to inhibit ERS in our previous report. Increased expression of AK054386, which might be mediated by activated NF-κB, resulted in sustained ERS and increased cell apoptosis and death in hepatic IRI mouse and cellular models. In contrast, AK054386 inhibition had protective effects on these models. Our data indicate that AK054386 and miR-199 are critical players in hepatic IRI, and we broadened the scope regarding ceRNA mechanisms. We hope that our results will improve the understanding of hepatic IRI and may provide potential therapeutic targets.

scholarly journals Dexmedetomidine Protects against Hepatic Ischemia-Reperfusion Injury by inhibiting Endoplasmic Reticulum Stress and Cell Apoptosis in Rats

2021 ◽  
Author(s):  
Hang Li ◽  
Jilang Tang ◽  
Weiqi Zhang ◽  
Liping Ai ◽  
Shixia Zhang
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Significant Difference ◽  
Hepatic Ischemia Reperfusion

Abstract Background: Hepatic ischemia-reperfusion injury (IRI) remains a major complication of liver surgery, dexmedetomidine (DEX) has a certain protective effect on liver during ischemia-reperfusion, but the underlying mechanisms are not fully understood. This study explored the protective effects of DEX and investigated whether DEX protects against hepatic IRI by inhibiting endoplasmic reticulum stress (ERS) and its downstream apoptotic pathway in a rat model. Methods: Thirty-six male Sprague-Dawley (SD) rats were divided into six groups: S, IR, DL, DM1, DH and DM2 group. Group S was subjected to laparotomy, and exposure of the portal triad without occlusion. I-R injury model was induced by clamping the portal vessels supplying the middle and left hepatic lobes for 30 min in IR, DL, DM1, DH and DM2 group. Then DL, DM1, DH group received DEX of 25 μg/kg, 50 μg/kg and 100 μg/kg intraperitoneally at 30 min before ischemia, respectively, DM2 group received 50 μg/kg DEX intraperitoneally 30 min after reperfusion, and IR group received normal saline. After 6 h of reperfusion, assessment of liver function, histopathology, oxidative stress was performed. The liver cell microstructure was detected by transmission electron microscopy. Hepatocyte apoptosis was determined by TUNEL assay. Real-time PCR, Western blotting were performed to analyze various ERS molecules. Results: We observed that DEX protected the liver by alleviating hepatocytes damage, reducing the content of ALT and MDA, increasing the activity of SOD, reducing the number of TUNEL-positive cells, down-regulating the expression of GRP-78, PERK, ATF-6, Caspase-12 mRNA, and p-PERK, p-IRE-1 α, CHOP proteins, up-regulating Bcl-2 protein. The effect of 50 μg/kg DEX is superior to 25 μg/kg DEX, but not significantly different from 100μg/kg DEX. There was no significant difference in the above monitoring indexes between DM1 and DM2 group. Conclusions: DEX protects the liver from IRI by inhibiting ERS and cell apoptosis. The protective effect of DEX was dose-dependent in a certain dose range, both DEX administered prior to ischemia and following reperfusion markedly reduced liver injury induced by hepatic IRI in mice.

scholarly journals d-Pinitol protects against endoplasmic reticulum stress and apoptosis in hepatic ischemia-reperfusion injury via modulation of AFT4-CHOP/GRP78 and caspase-3 signaling pathways

2021 ◽  
Vol 35 ◽  
pp. 205873842110320
Author(s):  
Lei Yan ◽  
Heng Luo ◽  
Xingsheng Li ◽  
Yongyong Li
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Reperfusion Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Binding Protein ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Pre Treatment ◽  
Hepatic Ischemia Reperfusion

Hepatic ischemia-reperfusion injury (IRI) is a major unavoidable clinical problem often accompanying various liver surgery and transplantation. d-Pinitol, a cyclic polyol, exhibits hepatoprotective efficacy. The objective of this study is to determine the possible mechanism of action of pinitol against endoplasmic reticulum (ER) stress regulation-mediated hepatic IRI and compare its effects with thymoquinone (TQ) in experimental rats. Male Sprague Dawley rats were pre-treated orally with either vehicle (DMSO) or d-Pinitol (5, 10, and 20 mg/kg) or TQ (30 mg/kg) for 21 days and subjected to 60 min of partial hepatic ischemia followed by 24 h of reperfusion. Pre-treatment with pinitol (10 and 20 mg/kg) effectively ( P  < 0.05) protected against IRI-induced hepatic damage reflected by attenuation of elevated oxidative stress and pro-inflammatory cytokines. Additionally, western blot and ELISA analyses suggested that pinitol significantly ( P  < 0.05) down-regulated expression of endoplasmic reticulum stress apoptotic markers, namely glucose-regulated protein (GRP)-78, CCAAT/enhancer-binding protein homologous protein (CHOP), activating transcription factor (AFT)-4 and -6α, X-box binding protein-1, and caspase-3, 9, and 12. Additionally, pinitol pre-treatment effectively ( P  < 0.05) improved mitochondrial function and phosphorylation of Extracellular signal-regulated kinase (ERK)-1/2 and p38. Pinitol markedly ( P  < 0.05) protected hepatic apoptosis determined by flow cytometry. Further, pinitol provided effective ( P  < 0.05) protection against hepatic histological and ultrastructural aberrations induced by IRI. TQ showed more pronounced protective effect against attenuation of IRI-induced hepatic injury as compared to d-Pinitol. Pinitol offered protection against endoplasmic reticulum stress-mediated phosphorylation of ERK1/2 and p38, thereby inhibiting AFT4-CHOP/GRP78 signaling response and caspase-3 induced hepatocellular apoptosis during hepatic ischemia-reperfusion insults. Thus, Pinitol can be considered as a viable option for the management of hepatic IRI.

scholarly journals Comparison of the protective effects of desflurane and propofol anesthesia in rats: a hepatic ischemia-reperfusion injury model

2013 ◽  
Vol 43 ◽  
pp. 592-598
Author(s):  
Ayca TAŞ TUNA ◽  
Cengiz Bekir DEMİREL ◽  
Yusuf ÜNAL ◽  
Aslıhan ÇAVUNT BAYRAKTAR ◽  
Demet YILMAZER ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Hepatic Ischemia ◽  
Injury Model ◽  
Hepatic Ischemia Reperfusion
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