Ras-related protein Rab-20 inhibition alleviates cerebral ischemia/reperfusion injury by inhibiting mitochondrial fission and dysfunction
Ras-related protein Rab-20 (Rab20) is induced in hypoxia and contributes to hypoxia-induced apoptosis. However, the role and mechanism of Rab20 in cerebral ischemia/reperfusion (I/R) injury need to be elucidated. We established a cerebral I/R injury model in the mice and an oxygen-glucose deprivatio...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.986710/full |
| _version_ | 1797985889221083136 |
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| author | Jia Guo Lu Zhang Yujie Bu Wenjuan Li Jianping Hu Jianxiong Li |
| author_facet | Jia Guo Lu Zhang Yujie Bu Wenjuan Li Jianping Hu Jianxiong Li |
| author_sort | Jia Guo |
| collection | DOAJ |
| description | Ras-related protein Rab-20 (Rab20) is induced in hypoxia and contributes to hypoxia-induced apoptosis. However, the role and mechanism of Rab20 in cerebral ischemia/reperfusion (I/R) injury need to be elucidated. We established a cerebral I/R injury model in the mice and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 cells to determine the effects of Rab20 in cerebral I/R injury. Rab20 expression was upregulated in mice after I/R and in HT22 cells after OGD/R. Upregulated Rab20 was mainly located in neurons. Rab20 inhibition significantly alleviated brain infarct volume, neurological deficits, and neuronal apoptosis in mice after I/R. Moreover, Rab20 knockdown significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Rab20 knockdown significantly alleviated OGD/R-induced mitochondrial fission by repressing mitochondrial dynamin-related protein 1 (Drp-1) recruitment and increasing Drp-1 (Ser637) phosphorylation and ameliorated mitochondrial dysfunction by reducing the mitochondrial reactive oxygen species (ROS) and cellular calcium accumulation and increasing the mitochondrial membrane potential. In addition, Rab20 knockdown significantly alleviated cytochrome c release from the mitochondria into the cytosol in HT22 cells after OGD/R. Rab20 contributes to cerebral I/R injury by regulating mitochondria-associated apoptosis pathways. Targeting Rab20 may be an attractive strategy for the treatment of cerebral I/R injury. |
| first_indexed | 2024-04-11T07:24:31Z |
| format | Article |
| id | doaj.art-9adc0e8e77174005b87609af995142a3 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-11T07:24:31Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-9adc0e8e77174005b87609af995142a32022-12-22T04:37:06ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-10-011510.3389/fnmol.2022.986710986710Ras-related protein Rab-20 inhibition alleviates cerebral ischemia/reperfusion injury by inhibiting mitochondrial fission and dysfunctionJia GuoLu ZhangYujie BuWenjuan LiJianping HuJianxiong LiRas-related protein Rab-20 (Rab20) is induced in hypoxia and contributes to hypoxia-induced apoptosis. However, the role and mechanism of Rab20 in cerebral ischemia/reperfusion (I/R) injury need to be elucidated. We established a cerebral I/R injury model in the mice and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 cells to determine the effects of Rab20 in cerebral I/R injury. Rab20 expression was upregulated in mice after I/R and in HT22 cells after OGD/R. Upregulated Rab20 was mainly located in neurons. Rab20 inhibition significantly alleviated brain infarct volume, neurological deficits, and neuronal apoptosis in mice after I/R. Moreover, Rab20 knockdown significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Rab20 knockdown significantly alleviated OGD/R-induced mitochondrial fission by repressing mitochondrial dynamin-related protein 1 (Drp-1) recruitment and increasing Drp-1 (Ser637) phosphorylation and ameliorated mitochondrial dysfunction by reducing the mitochondrial reactive oxygen species (ROS) and cellular calcium accumulation and increasing the mitochondrial membrane potential. In addition, Rab20 knockdown significantly alleviated cytochrome c release from the mitochondria into the cytosol in HT22 cells after OGD/R. Rab20 contributes to cerebral I/R injury by regulating mitochondria-associated apoptosis pathways. Targeting Rab20 may be an attractive strategy for the treatment of cerebral I/R injury.https://www.frontiersin.org/articles/10.3389/fnmol.2022.986710/fullRab20cerebral ischemia/reperfusionmitochondriamitochondrial fissionapoptosis |
| spellingShingle | Jia Guo Lu Zhang Yujie Bu Wenjuan Li Jianping Hu Jianxiong Li Ras-related protein Rab-20 inhibition alleviates cerebral ischemia/reperfusion injury by inhibiting mitochondrial fission and dysfunction Frontiers in Molecular Neuroscience Rab20 cerebral ischemia/reperfusion mitochondria mitochondrial fission apoptosis |
| title | Ras-related protein Rab-20 inhibition alleviates cerebral ischemia/reperfusion injury by inhibiting mitochondrial fission and dysfunction |
| title_full | Ras-related protein Rab-20 inhibition alleviates cerebral ischemia/reperfusion injury by inhibiting mitochondrial fission and dysfunction |
| title_fullStr | Ras-related protein Rab-20 inhibition alleviates cerebral ischemia/reperfusion injury by inhibiting mitochondrial fission and dysfunction |
| title_full_unstemmed | Ras-related protein Rab-20 inhibition alleviates cerebral ischemia/reperfusion injury by inhibiting mitochondrial fission and dysfunction |
| title_short | Ras-related protein Rab-20 inhibition alleviates cerebral ischemia/reperfusion injury by inhibiting mitochondrial fission and dysfunction |
| title_sort | ras related protein rab 20 inhibition alleviates cerebral ischemia reperfusion injury by inhibiting mitochondrial fission and dysfunction |
| topic | Rab20 cerebral ischemia/reperfusion mitochondria mitochondrial fission apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.986710/full |
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