Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway
Abstract 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 stu...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-29907-z |
| _version_ | 1797864737265942528 |
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| author | Wanli Ji Yaoxin Ren Xiaolian Wei Xiangxiang Ding Yihan Dong Bin Yuan |
| author_facet | Wanli Ji Yaoxin Ren Xiaolian Wei Xiangxiang Ding Yihan Dong Bin Yuan |
| author_sort | Wanli Ji |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T22:56:56Z |
| format | Article |
| id | doaj.art-16b1d8d6cde1446cabace872dc16e293 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T22:56:56Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-16b1d8d6cde1446cabace872dc16e2932023-03-22T11:11:45ZengNature PortfolioScientific Reports2045-23222023-02-0113111110.1038/s41598-023-29907-zIschemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathwayWanli Ji0Yaoxin Ren1Xiaolian Wei2Xiangxiang Ding3Yihan Dong4Bin Yuan5Department of Neurology II, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical UniversityDepartment of Neurology II, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical UniversityDepartment of Neurology II, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical UniversityDepartment of Neurology II, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical UniversityDepartment of Neurology II, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical UniversityDepartment of Neurology II, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical UniversityAbstract 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.https://doi.org/10.1038/s41598-023-29907-z |
| spellingShingle | Wanli Ji Yaoxin Ren Xiaolian Wei Xiangxiang Ding Yihan Dong Bin Yuan Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-023-29907-z |
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