MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathway
Brain microvascular endothelial cells (BMECs) dysfunction is related to the pathogenesis of neurovascular complication of diabetes mellitus that adversely lead to various CNS disorders. Mitoquinone (MitoQ) is a mitochondria targeted antioxidant that exerts multiple protective effects in many oxidati...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Journal of Pharmacological Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861320301055 |
| _version_ | 1818644686555840512 |
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| author | Min-yan Yang Zhen Fan Zhao Zhang Jin Fan |
| author_facet | Min-yan Yang Zhen Fan Zhao Zhang Jin Fan |
| author_sort | Min-yan Yang |
| collection | DOAJ |
| description | Brain microvascular endothelial cells (BMECs) dysfunction is related to the pathogenesis of neurovascular complication of diabetes mellitus that adversely lead to various CNS disorders. Mitoquinone (MitoQ) is a mitochondria targeted antioxidant that exerts multiple protective effects in many oxidative damage-related diseases. In this study, we determined the protective effects of MitoQ on high glucose (HG)-induced BMECs injury and investigated the underlying mechanism. We found that HG significantly reduced the expression of Nrf2 and HO-1, decreased mitochondrial membrane potential, increased intracellular and mitochondrial reactive oxygen species (ROS) generation, induced cytoskeletal damage and apoptosis in BMECs. In addition, Mito tempol, a mitochondrial ROS scavenger, significantly reduced HG-induced mitochondrial ROS production and attenuated cytoskeletal damage and cell apoptosis, suggesting MtROS production was involved in HG-induced BMECs injury. Moreover, we found that MitoQ treatment significantly upregulated the expression of Nrf2 and HO-1 in HG-induced BMECs, which is accompanied by improved mitochondrial membrane potential and decreased MtROS production. Meanwhile, MitoQ treatment also remarkably attenuated HG-induced cytoskeletal damage and cell apoptosis in BMECs. However, inhibitor of Nrf2 with ML385 impaired the protective effects of MitoQ in HG-induced BMECs. In conclusion, our results suggest that MitoQ exerts protective effect on HG-induced BMECs injury via activating Nrf2/HO-1 pathway. |
| first_indexed | 2024-12-17T00:18:48Z |
| format | Article |
| id | doaj.art-25c25d24eb614c8082e1f05f6b0251ad |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-17T00:18:48Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-25c25d24eb614c8082e1f05f6b0251ad2022-12-21T22:10:37ZengElsevierJournal of Pharmacological Sciences1347-86132021-01-011451105114MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathwayMin-yan Yang0Zhen Fan1Zhao Zhang2Jin Fan3Department of Internal Medicine, The Fourth People's Hospital of Chengdu, Chengdu, Sichuan, ChinaDepartment of Geriatrics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, ChinaDepartment of Emergency, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, ChinaDepartment of Neurology, The General Hospital of Western Theater Command, Chendu, Sichuan, China; Corresponding author.Brain microvascular endothelial cells (BMECs) dysfunction is related to the pathogenesis of neurovascular complication of diabetes mellitus that adversely lead to various CNS disorders. Mitoquinone (MitoQ) is a mitochondria targeted antioxidant that exerts multiple protective effects in many oxidative damage-related diseases. In this study, we determined the protective effects of MitoQ on high glucose (HG)-induced BMECs injury and investigated the underlying mechanism. We found that HG significantly reduced the expression of Nrf2 and HO-1, decreased mitochondrial membrane potential, increased intracellular and mitochondrial reactive oxygen species (ROS) generation, induced cytoskeletal damage and apoptosis in BMECs. In addition, Mito tempol, a mitochondrial ROS scavenger, significantly reduced HG-induced mitochondrial ROS production and attenuated cytoskeletal damage and cell apoptosis, suggesting MtROS production was involved in HG-induced BMECs injury. Moreover, we found that MitoQ treatment significantly upregulated the expression of Nrf2 and HO-1 in HG-induced BMECs, which is accompanied by improved mitochondrial membrane potential and decreased MtROS production. Meanwhile, MitoQ treatment also remarkably attenuated HG-induced cytoskeletal damage and cell apoptosis in BMECs. However, inhibitor of Nrf2 with ML385 impaired the protective effects of MitoQ in HG-induced BMECs. In conclusion, our results suggest that MitoQ exerts protective effect on HG-induced BMECs injury via activating Nrf2/HO-1 pathway.http://www.sciencedirect.com/science/article/pii/S1347861320301055MitoQNrf2Mitochondrial ROSBrain microvascular endothelial cellsDiabetes |
| spellingShingle | Min-yan Yang Zhen Fan Zhao Zhang Jin Fan MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathway Journal of Pharmacological Sciences MitoQ Nrf2 Mitochondrial ROS Brain microvascular endothelial cells Diabetes |
| title | MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathway |
| title_full | MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathway |
| title_fullStr | MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathway |
| title_full_unstemmed | MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathway |
| title_short | MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathway |
| title_sort | mitoq protects against high glucose induced brain microvascular endothelial cells injury via the nrf2 ho 1 pathway |
| topic | MitoQ Nrf2 Mitochondrial ROS Brain microvascular endothelial cells Diabetes |
| url | http://www.sciencedirect.com/science/article/pii/S1347861320301055 |
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