Overexpression of Mitochondrial Ferritin Enhances Blood–Brain Barrier Integrity Following Ischemic Stroke in Mice by Maintaining Iron Homeostasis in Endothelial Cells
Blood–brain barrier (BBB) breakdown, a characteristic feature of ischemic stroke, contributes to poor patient outcomes. Brain microvascular endothelial cells (BMVECs) are a key component of the BBB and dysfunction or death of these cells following cerebral ischemia reperfusion (I/R) injury can disru...
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MDPI AG
2022-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/7/1257 |
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| author | Peina Wang Qianqian Ren Mengtong Shi Yuanyuan Liu Huiyuan Bai Yan-Zhong Chang |
| author_facet | Peina Wang Qianqian Ren Mengtong Shi Yuanyuan Liu Huiyuan Bai Yan-Zhong Chang |
| author_sort | Peina Wang |
| collection | DOAJ |
| description | Blood–brain barrier (BBB) breakdown, a characteristic feature of ischemic stroke, contributes to poor patient outcomes. Brain microvascular endothelial cells (BMVECs) are a key component of the BBB and dysfunction or death of these cells following cerebral ischemia reperfusion (I/R) injury can disrupt the BBB, leading to leukocyte infiltration, brain edema and intracerebral hemorrhage. We previously demonstrated that mitochondrial ferritin (FtMt) can alleviate I/R-induced neuronal ferroptosis by inhibiting inflammation-regulated iron deposition. However, whether FtMt is involved in BBB disruption during cerebral I/R is still unknown. In the present study, we found that FtMt expression in BMVECs is upregulated after I/R and overexpression of FtMt attenuates I/R-induced BBB disruption. Mechanistically, we found that FtMt prevents tight junction loss and apoptosis by inhibiting iron dysregulation and reactive oxygen species (ROS) accumulation in I/R-treated BMVECs. Chelating excess iron with deferoxamine alleviates apoptosis in the brain endothelial cell line bEnd.3 under oxygen glucose deprivation followed by reoxygenation (OGD/R) insult. In summary, our data identify a previously unexplored effect for FtMt in the BBB and provide evidence that iron-mediated oxidative stress in BMVECs is an early cause of BMVECs damage and BBB breakdown in ischemic stroke. |
| first_indexed | 2024-03-09T10:23:01Z |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T10:23:01Z |
| publishDate | 2022-06-01 |
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| spelling | doaj.art-34df3e8c8bd347fbbab69e6a01acfcd32023-12-01T21:49:31ZengMDPI AGAntioxidants2076-39212022-06-01117125710.3390/antiox11071257Overexpression of Mitochondrial Ferritin Enhances Blood–Brain Barrier Integrity Following Ischemic Stroke in Mice by Maintaining Iron Homeostasis in Endothelial CellsPeina Wang0Qianqian Ren1Mengtong Shi2Yuanyuan Liu3Huiyuan Bai4Yan-Zhong Chang5Laboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Ministry of Education Key Laboratory of Molecular and Cellular Biology, College of Life Science, Hebei Normal University, Shijiazhuang 050024, ChinaLaboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Ministry of Education Key Laboratory of Molecular and Cellular Biology, College of Life Science, Hebei Normal University, Shijiazhuang 050024, ChinaLaboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Ministry of Education Key Laboratory of Molecular and Cellular Biology, College of Life Science, Hebei Normal University, Shijiazhuang 050024, ChinaLaboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Ministry of Education Key Laboratory of Molecular and Cellular Biology, College of Life Science, Hebei Normal University, Shijiazhuang 050024, ChinaLaboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Ministry of Education Key Laboratory of Molecular and Cellular Biology, College of Life Science, Hebei Normal University, Shijiazhuang 050024, ChinaLaboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Ministry of Education Key Laboratory of Molecular and Cellular Biology, College of Life Science, Hebei Normal University, Shijiazhuang 050024, ChinaBlood–brain barrier (BBB) breakdown, a characteristic feature of ischemic stroke, contributes to poor patient outcomes. Brain microvascular endothelial cells (BMVECs) are a key component of the BBB and dysfunction or death of these cells following cerebral ischemia reperfusion (I/R) injury can disrupt the BBB, leading to leukocyte infiltration, brain edema and intracerebral hemorrhage. We previously demonstrated that mitochondrial ferritin (FtMt) can alleviate I/R-induced neuronal ferroptosis by inhibiting inflammation-regulated iron deposition. However, whether FtMt is involved in BBB disruption during cerebral I/R is still unknown. In the present study, we found that FtMt expression in BMVECs is upregulated after I/R and overexpression of FtMt attenuates I/R-induced BBB disruption. Mechanistically, we found that FtMt prevents tight junction loss and apoptosis by inhibiting iron dysregulation and reactive oxygen species (ROS) accumulation in I/R-treated BMVECs. Chelating excess iron with deferoxamine alleviates apoptosis in the brain endothelial cell line bEnd.3 under oxygen glucose deprivation followed by reoxygenation (OGD/R) insult. In summary, our data identify a previously unexplored effect for FtMt in the BBB and provide evidence that iron-mediated oxidative stress in BMVECs is an early cause of BMVECs damage and BBB breakdown in ischemic stroke.https://www.mdpi.com/2076-3921/11/7/1257blood–brain barrierischemic strokemitochondrial ferritinironendothelial cells |
| spellingShingle | Peina Wang Qianqian Ren Mengtong Shi Yuanyuan Liu Huiyuan Bai Yan-Zhong Chang Overexpression of Mitochondrial Ferritin Enhances Blood–Brain Barrier Integrity Following Ischemic Stroke in Mice by Maintaining Iron Homeostasis in Endothelial Cells Antioxidants blood–brain barrier ischemic stroke mitochondrial ferritin iron endothelial cells |
| title | Overexpression of Mitochondrial Ferritin Enhances Blood–Brain Barrier Integrity Following Ischemic Stroke in Mice by Maintaining Iron Homeostasis in Endothelial Cells |
| title_full | Overexpression of Mitochondrial Ferritin Enhances Blood–Brain Barrier Integrity Following Ischemic Stroke in Mice by Maintaining Iron Homeostasis in Endothelial Cells |
| title_fullStr | Overexpression of Mitochondrial Ferritin Enhances Blood–Brain Barrier Integrity Following Ischemic Stroke in Mice by Maintaining Iron Homeostasis in Endothelial Cells |
| title_full_unstemmed | Overexpression of Mitochondrial Ferritin Enhances Blood–Brain Barrier Integrity Following Ischemic Stroke in Mice by Maintaining Iron Homeostasis in Endothelial Cells |
| title_short | Overexpression of Mitochondrial Ferritin Enhances Blood–Brain Barrier Integrity Following Ischemic Stroke in Mice by Maintaining Iron Homeostasis in Endothelial Cells |
| title_sort | overexpression of mitochondrial ferritin enhances blood brain barrier integrity following ischemic stroke in mice by maintaining iron homeostasis in endothelial cells |
| topic | blood–brain barrier ischemic stroke mitochondrial ferritin iron endothelial cells |
| url | https://www.mdpi.com/2076-3921/11/7/1257 |
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