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Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway

Macrophage migration inhibitory factor (MIF) is an immune mediator associated with inflammation, which is upregulated after ischemia in brain tissue. ISO-1 is a potent inhibitor of MIF tautomerase and can protect neurons by reducing the permeability of blood brain barrier (BBB). In this study, we in...

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Autores principales: Ji, Wanli, Ren, Yaoxin, Wei, Xiaolian, Ding, Xiangxiang, Dong, Yihan, Yuan, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935850/
https://www.ncbi.nlm.nih.gov/pubmed/36797398
http://dx.doi.org/10.1038/s41598-023-29907-z
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author Ji, Wanli
Ren, Yaoxin
Wei, Xiaolian
Ding, Xiangxiang
Dong, Yihan
Yuan, Bin
author_facet Ji, Wanli
Ren, Yaoxin
Wei, Xiaolian
Ding, Xiangxiang
Dong, Yihan
Yuan, Bin
author_sort Ji, Wanli
collection PubMed
description Macrophage migration inhibitory factor (MIF) is an immune mediator associated with inflammation, which is upregulated after ischemia in brain tissue. ISO-1 is a potent inhibitor of MIF tautomerase and can protect neurons by reducing the permeability of blood brain barrier (BBB). In this study, we investigated the role of ISO-1 in cerebral ischemia/reperfusion injury by establishing a model of middle cerebral artery occlusion/reperfusion in rats. Rats were randomly divided into four groups: the sham operation group, the ISO-1group, the cerebral I/R group, and the ISO-1 + I/R group. We assessed the degree of neurological deficit in each group and measured the volume of cerebral infarction. We detected the expression of MIF in the core necrotic area and penumbra. We detected the expression of apoptosis-related proteins, apoptosis-inducing factor (AIF), endonuclease G (EndoG) and cytochrome c oxidase-IV (COX-IV) in the ischemic penumbra region. The results showed that MIF was expressed in the ischemic penumbra, while the injection of ISO-1 was able to alleviate neurological damage and reduce the infarction volume. In the cerebral ischemic penumbra region, ISO-1 could reduce the expression of Bax and Caspase3 and inhibit the displacement of AIF and EndoG to the nucleus simultaneously. Besides, ISO-1 also exhibited the ability to reduce apoptosis. In summary, ISO-1 may inhibit neuronal apoptosis through the endogenous mitochondrial pathway and reduce the injury of brain I/R after ischemic stroke.
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spelling pubmed-99358502023-02-18 Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway Ji, Wanli Ren, Yaoxin Wei, Xiaolian Ding, Xiangxiang Dong, Yihan Yuan, Bin Sci Rep Article Macrophage migration inhibitory factor (MIF) is an immune mediator associated with inflammation, which is upregulated after ischemia in brain tissue. ISO-1 is a potent inhibitor of MIF tautomerase and can protect neurons by reducing the permeability of blood brain barrier (BBB). In this study, we investigated the role of ISO-1 in cerebral ischemia/reperfusion injury by establishing a model of middle cerebral artery occlusion/reperfusion in rats. Rats were randomly divided into four groups: the sham operation group, the ISO-1group, the cerebral I/R group, and the ISO-1 + I/R group. We assessed the degree of neurological deficit in each group and measured the volume of cerebral infarction. We detected the expression of MIF in the core necrotic area and penumbra. We detected the expression of apoptosis-related proteins, apoptosis-inducing factor (AIF), endonuclease G (EndoG) and cytochrome c oxidase-IV (COX-IV) in the ischemic penumbra region. The results showed that MIF was expressed in the ischemic penumbra, while the injection of ISO-1 was able to alleviate neurological damage and reduce the infarction volume. In the cerebral ischemic penumbra region, ISO-1 could reduce the expression of Bax and Caspase3 and inhibit the displacement of AIF and EndoG to the nucleus simultaneously. Besides, ISO-1 also exhibited the ability to reduce apoptosis. In summary, ISO-1 may inhibit neuronal apoptosis through the endogenous mitochondrial pathway and reduce the injury of brain I/R after ischemic stroke. Nature Publishing Group UK 2023-02-16 /pmc/articles/PMC9935850/ /pubmed/36797398 http://dx.doi.org/10.1038/s41598-023-29907-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ji, Wanli
Ren, Yaoxin
Wei, Xiaolian
Ding, Xiangxiang
Dong, Yihan
Yuan, Bin
Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway
title Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway
title_full Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway
title_fullStr Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway
title_full_unstemmed Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway
title_short Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway
title_sort ischemic stroke protected by iso-1 inhibition of apoptosis via mitochondrial pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935850/
https://www.ncbi.nlm.nih.gov/pubmed/36797398
http://dx.doi.org/10.1038/s41598-023-29907-z
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