Omega-3 polyunsaturated fatty acids inhibit the increase in cytokines and chemotactic factors induced in vitro by lymph fluid from an intestinal ischemia-reperfusion injury model

Intestinal epithelial oxidative stress and apoptosis constitute key pathogenic mechanisms underlying intestinal ischemia/reperfusion (I/R) injury. We previously reported that the adaptor 66 kDa isoform of the adaptor molecule ShcA (p66Shc)-mediated pro-apoptotic pathway was activated after intestinal I/R. However, the upstream regulators of the p66Shc pathway involved in intestinal I/R remain to be fully identified. Here, we focused on the role of a prolyl-isomerase, peptidyl–prolyl cis–trans isomerase (Pin1), in the regulation of p66Shc activity during intestinal I/R. Intestinal I/R was induced in rats by superior mesenteric artery (SMA) occlusion. Juglone (Pin1 inhibitor) or vehicle was injected intraperitoneally before I/R challenge. Caco-2 cells were exposed to hypoxia/reoxygenation (H/R) in vitro to simulate an in vivo I/R model. We found that p66Shc was significantly up-regulated in the I/R intestine and that this up-regulation resulted in the accumulation of intestinal mitochondrial reactive oxygen species (ROS) and massive epithelial apoptosis. Moreover, intestinal I/R resulted in elevated protein expression and enzyme activity of Pin1 as well as increased interaction between Pin1 and p66Shc. This Pin1 activation was responsible for the translocation of p66Shc to the mitochondria during intestinal I/R, as Pin1 suppression by juglone or siRNA markedly blunted p66Shc mitochondrial translocation and the subsequent ROS generation and cellular apoptosis. Additionally, Pin1 inhibition alleviated gut damage and secondary lung injury, leading to improvement of survival after I/R. Collectively, our findings demonstrate for the first time that Pin1 inhibition protects against intestinal I/R injury, which could be partially attributed to the p66Shc-mediated mitochondrial apoptosis pathway. This may represent a novel prophylactic target for intestinal I/R injury.

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Qingchang Mixture Prevents the Intestinal Ischemia-reperfusion Injury Through TLR4/NF-kB Pathway

10.21203/rs.3.rs-136204/v1 ◽

2021 ◽

Author(s):

Meng Wang ◽

Yong Zhu ◽

Shujuan Liu ◽

Zhaochun Tian ◽

Pengfei Zhu ◽

...

Keyword(s):

Chinese Medicine ◽

Intestinal Ischemia ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Intestinal Epithelial ◽

Human Intestinal Epithelial Cells ◽

Molecule Inhibitor ◽

Apoptosis Detection ◽

Intestinal Ischemia Reperfusion

Abstract Background: This study was performed to determine the protection and molecular responses of Chinese medicine Qingchang mixture on intestinal ischemia-reperfusion (IR) injury.Methods: The rat intestinal IR model was prepared. Intestinal ischemic injury was evaluated by the HE staining, biochemical assay and western blot. In addition, human intestinal epithelial cells (IEC-6) hypoxia-reoxygenation (HR) in vitro model was prepared. The viability and apoptosis of IEC-6 cells were measured by CCK8 and apoptosis detection. TAK242 or PDTC was used as the small molecule inhibitor of TLR4 or NF-κB.Results: Compared with the IR group, the pretreatment of Qingchang mixture relieved the morphological damage, oxidative stress, inflammatory response and barrier function damage of small intestine tissue. IR significantly increased the expression of TLR4 and NF-κB, while the pretreatment of Qingchang mixture inhibited the expression of TLR4 and NF-κB. Furthermore, the pretreatment of Qingchang mixture, TAK242 or PDTC effectively improved the viability, and hindered apoptosis of the HR-induced IEC-6 cells.Conclusions: Chinese medicine Qingchang mixture prevents the intestinal IR injury through TLR4/NF-kB pathway.

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Effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia−reperfusion injury

Pediatric Surgery International ◽

10.1007/s00383-012-3144-0 ◽

2012 ◽

Vol 28 (9) ◽

pp. 913-918 ◽

Cited By ~ 9

Author(s):

Atsuhiro Arisue ◽

Naoki Shimojima ◽

Masayuki Tomiya ◽

Takayuki Shimizu ◽

Daisuke Harada ◽

...

Keyword(s):

Oxidative Stress ◽

Reperfusion Injury ◽

Rat Model ◽

Lipid Emulsion ◽

Intestinal Ischemia ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Omega 3 ◽

Intestinal Ischemia Reperfusion

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Faculty Opinions recommendation of Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1018778.212487 ◽

2004 ◽

Author(s):

Richard L Stevens

Keyword(s):

Reperfusion Injury ◽

Intestinal Ischemia ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Igm Antibody ◽

Intestinal Ischemia Reperfusion

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Role of JNK phosphorylation in intestinal ischemia/reperfusion injury in mice

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2010.00140 ◽

2010 ◽

Vol 30 (2) ◽

pp. 140-143

Author(s):

De-yi ZHENG ◽

Jian-ming WNAG ◽

Yi-tao JIA ◽

Jin-feng FU ◽

Kai-yang LU ◽

...

Keyword(s):

Reperfusion Injury ◽

Intestinal Ischemia ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Intestinal Ischemia Reperfusion

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Overexpression of SP1 restores autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway

Journal of Inflammation ◽

10.1186/s12950-021-00270-y ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Chong Huang ◽

Yan Chen ◽

Bin Lai ◽

Yan-Xia Chen ◽

Cheng-Yun Xu ◽

...

Keyword(s):

Reperfusion Injury ◽

Cell Apoptosis ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Renal Ischemia ◽

Akt Pathway ◽

Acute Renal Injury ◽

Injury Model ◽

Renal Ischemia Reperfusion Injury

Abstract Background Acute kidney injury (AKI) is a major kidney disease with poor clinical outcome. SP1, a well-known transcription factor, plays a critical role in AKI and subsequent kidney repair through the regulation of various cell biologic processes. However, the underlying mechanism of SP1 in these pathological processes remain largely unknown. Methods An in vitro HK-2 cells with anoxia-reoxygenation injury model (In vitro simulated ischemic injury disease) and an in vivo rat renal ischemia-reperfusion injury model were used in this study. The expression levels of SP1, miR-205 and PTEN were detected by RT-qPCR, and the protein expression levels of SP1, p62, PTEN, AKT, p-AKT, LC3II, LC3I and Beclin-1 were assayed by western blot. Cell proliferation was assessed by MTT assay, and the cell apoptosis was detected by flow cytometry. The secretions of IL-6 and TNF-α were detected by ELISA. The targeted relationship between miR-205 and PTEN was confirmed by dual luciferase report assay. The expression and positioning of LC-3 were observed by immunofluorescence staining. TUNEL staining was used to detect cell apoptosis and immunohistochemical analysis was used to evaluate the expression of SP1 in renal tissue after ischemia-reperfusion injury in rats. Results The expression of PTEN was upregulated while SP1 and miR-205 were downregulated in renal ischemia-reperfusion injury. Overexpression of SP1 protected renal tubule cell against injury induced by ischemia-reperfusion via miR-205/PTEN/Akt pathway mediated autophagy. Overexpression of SP1 attenuated renal ischemia-reperfusion injury in rats. Conclusions SP1 overexpression restored autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway.

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