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Ischemic Postconditioning-Mediated DJ-1 Activation Mitigate Intestinal Mucosa Injury Induced by Myocardial Ischemia Reperfusion in Rats Through Keap1/Nrf2 Pathway

Intestinal mucosal barrier dysfunction induced by myocardial ischemia reperfusion (IR) injury often leads to adverse cardiovascular outcomes after myocardial infarction. Early detection and prevention of remote intestinal injury following myocardial IR may help to estimate and improve prognosis afte...

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Autores principales: Chen, Rong, Li, Wei, Qiu, Zhen, Zhou, Qin, Zhang, Yuan, Li, Wen-yuan, Ding, Ke, Meng, Qing-tao, Xia, Zhong-yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119885/
https://www.ncbi.nlm.nih.gov/pubmed/33996908
http://dx.doi.org/10.3389/fmolb.2021.655619
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author Chen, Rong
Li, Wei
Qiu, Zhen
Zhou, Qin
Zhang, Yuan
Li, Wen-yuan
Ding, Ke
Meng, Qing-tao
Xia, Zhong-yuan
author_facet Chen, Rong
Li, Wei
Qiu, Zhen
Zhou, Qin
Zhang, Yuan
Li, Wen-yuan
Ding, Ke
Meng, Qing-tao
Xia, Zhong-yuan
author_sort Chen, Rong
collection PubMed
description Intestinal mucosal barrier dysfunction induced by myocardial ischemia reperfusion (IR) injury often leads to adverse cardiovascular outcomes after myocardial infarction. Early detection and prevention of remote intestinal injury following myocardial IR may help to estimate and improve prognosis after acute myocardial infarction (AMI). This study investigated the protective effect of myocardial ischemic postconditioning (IPo) on intestinal barrier injury induced by myocardial IR and the underlying cellular signaling mechanisms with a focus on the DJ-1. Adult SD rats were subjected to unilateral myocardial IR with or without ischemic postconditioning. After 30 min of ischemia and 120 min of reperfusion, heart tissue, intestine, and blood were collected for subsequent examination. The outcome measures were (i) intestinal histopathology, (ii) intestinal barrier function and inflammatory responses, (iii) apoptosis and oxidative stress, and (iv) cellular signaling changes. IPo significantly attenuated intestinal injury induced by myocardial IR. Furthermore, IPo significantly increased DJ-1, nuclear Nrf2, NQO1, and HO-1 expression in the intestine and inhibited IR-induced apoptosis and oxidative stress. The protective effect of IPo was abolished by the knockdown of DJ-1. Conversely, the overexpression of DJ-1 provided a protective effect similar to that of IPo. Our data indicate that IPo protects the intestine against myocardial IR, which is likely mediated by the upregulation of DJ-1/Nrf2 pathway.
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spelling pubmed-81198852021-05-15 Ischemic Postconditioning-Mediated DJ-1 Activation Mitigate Intestinal Mucosa Injury Induced by Myocardial Ischemia Reperfusion in Rats Through Keap1/Nrf2 Pathway Chen, Rong Li, Wei Qiu, Zhen Zhou, Qin Zhang, Yuan Li, Wen-yuan Ding, Ke Meng, Qing-tao Xia, Zhong-yuan Front Mol Biosci Molecular Biosciences Intestinal mucosal barrier dysfunction induced by myocardial ischemia reperfusion (IR) injury often leads to adverse cardiovascular outcomes after myocardial infarction. Early detection and prevention of remote intestinal injury following myocardial IR may help to estimate and improve prognosis after acute myocardial infarction (AMI). This study investigated the protective effect of myocardial ischemic postconditioning (IPo) on intestinal barrier injury induced by myocardial IR and the underlying cellular signaling mechanisms with a focus on the DJ-1. Adult SD rats were subjected to unilateral myocardial IR with or without ischemic postconditioning. After 30 min of ischemia and 120 min of reperfusion, heart tissue, intestine, and blood were collected for subsequent examination. The outcome measures were (i) intestinal histopathology, (ii) intestinal barrier function and inflammatory responses, (iii) apoptosis and oxidative stress, and (iv) cellular signaling changes. IPo significantly attenuated intestinal injury induced by myocardial IR. Furthermore, IPo significantly increased DJ-1, nuclear Nrf2, NQO1, and HO-1 expression in the intestine and inhibited IR-induced apoptosis and oxidative stress. The protective effect of IPo was abolished by the knockdown of DJ-1. Conversely, the overexpression of DJ-1 provided a protective effect similar to that of IPo. Our data indicate that IPo protects the intestine against myocardial IR, which is likely mediated by the upregulation of DJ-1/Nrf2 pathway. Frontiers Media S.A. 2021-04-30 /pmc/articles/PMC8119885/ /pubmed/33996908 http://dx.doi.org/10.3389/fmolb.2021.655619 Text en Copyright © 2021 Chen, Li, Qiu, Zhou, Zhang, Li, Ding, Meng and Xia. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Chen, Rong
Li, Wei
Qiu, Zhen
Zhou, Qin
Zhang, Yuan
Li, Wen-yuan
Ding, Ke
Meng, Qing-tao
Xia, Zhong-yuan
Ischemic Postconditioning-Mediated DJ-1 Activation Mitigate Intestinal Mucosa Injury Induced by Myocardial Ischemia Reperfusion in Rats Through Keap1/Nrf2 Pathway
title Ischemic Postconditioning-Mediated DJ-1 Activation Mitigate Intestinal Mucosa Injury Induced by Myocardial Ischemia Reperfusion in Rats Through Keap1/Nrf2 Pathway
title_full Ischemic Postconditioning-Mediated DJ-1 Activation Mitigate Intestinal Mucosa Injury Induced by Myocardial Ischemia Reperfusion in Rats Through Keap1/Nrf2 Pathway
title_fullStr Ischemic Postconditioning-Mediated DJ-1 Activation Mitigate Intestinal Mucosa Injury Induced by Myocardial Ischemia Reperfusion in Rats Through Keap1/Nrf2 Pathway
title_full_unstemmed Ischemic Postconditioning-Mediated DJ-1 Activation Mitigate Intestinal Mucosa Injury Induced by Myocardial Ischemia Reperfusion in Rats Through Keap1/Nrf2 Pathway
title_short Ischemic Postconditioning-Mediated DJ-1 Activation Mitigate Intestinal Mucosa Injury Induced by Myocardial Ischemia Reperfusion in Rats Through Keap1/Nrf2 Pathway
title_sort ischemic postconditioning-mediated dj-1 activation mitigate intestinal mucosa injury induced by myocardial ischemia reperfusion in rats through keap1/nrf2 pathway
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119885/
https://www.ncbi.nlm.nih.gov/pubmed/33996908
http://dx.doi.org/10.3389/fmolb.2021.655619
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