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MiR-34a Interacts with Cytochrome c and Shapes Stroke Outcomes

Blood-brain barrier (BBB) dysfunction occurs in cerebrovascular diseases and neurodegenerative disorders such as stroke. Opening of the BBB during a stroke has a negative impact on acute outcomes. We have recently demonstrated that miR-34a regulates the BBB by targeting cytochrome c (CYC) in vitro....

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Autores principales: Hu, Heng, Hone, Emily A., Provencher, Edward A. P., Sprowls, Samuel A., Farooqi, Imran, Corbin, Deborah R., Sarkar, Saumyendra N., Hollander, John M., Lockman, Paul R., Simpkins, James W., Ren, Xuefang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040038/
https://www.ncbi.nlm.nih.gov/pubmed/32094435
http://dx.doi.org/10.1038/s41598-020-59997-y
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author Hu, Heng
Hone, Emily A.
Provencher, Edward A. P.
Sprowls, Samuel A.
Farooqi, Imran
Corbin, Deborah R.
Sarkar, Saumyendra N.
Hollander, John M.
Lockman, Paul R.
Simpkins, James W.
Ren, Xuefang
author_facet Hu, Heng
Hone, Emily A.
Provencher, Edward A. P.
Sprowls, Samuel A.
Farooqi, Imran
Corbin, Deborah R.
Sarkar, Saumyendra N.
Hollander, John M.
Lockman, Paul R.
Simpkins, James W.
Ren, Xuefang
author_sort Hu, Heng
collection PubMed
description Blood-brain barrier (BBB) dysfunction occurs in cerebrovascular diseases and neurodegenerative disorders such as stroke. Opening of the BBB during a stroke has a negative impact on acute outcomes. We have recently demonstrated that miR-34a regulates the BBB by targeting cytochrome c (CYC) in vitro. To investigate the role of miR-34a in a stroke, we purified primary cerebrovascular endothelial cells (pCECs) from mouse brains following 1 h transient middle cerebral artery occlusion (tMCAO) and measured real-time PCR to detect miR-34a levels. We demonstrate that the miR-34a levels are elevated in pCECs from tMCAO mice at the time point of BBB opening following 1 h tMCAO and reperfusion. Interestingly, knockout of miR-34a significantly reduces BBB permeability, alleviates disruption of tight junctions, and improves stroke outcomes compared to wild-type (WT) controls. CYC is decreased in the ischemic hemispheres and pCECs from WT but not in miR-34a(−/−) mice following stroke reperfusion. We further confirmed CYC is a target of miR-34a by a dural luciferase reporter gene assay in vitro. Our study provides the first description of miR-34a affecting stroke outcomes and may lead to discovery of new mechanisms and treatments for cerebrovascular and neurodegenerative diseases such as stroke.
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spelling pubmed-70400382020-03-03 MiR-34a Interacts with Cytochrome c and Shapes Stroke Outcomes Hu, Heng Hone, Emily A. Provencher, Edward A. P. Sprowls, Samuel A. Farooqi, Imran Corbin, Deborah R. Sarkar, Saumyendra N. Hollander, John M. Lockman, Paul R. Simpkins, James W. Ren, Xuefang Sci Rep Article Blood-brain barrier (BBB) dysfunction occurs in cerebrovascular diseases and neurodegenerative disorders such as stroke. Opening of the BBB during a stroke has a negative impact on acute outcomes. We have recently demonstrated that miR-34a regulates the BBB by targeting cytochrome c (CYC) in vitro. To investigate the role of miR-34a in a stroke, we purified primary cerebrovascular endothelial cells (pCECs) from mouse brains following 1 h transient middle cerebral artery occlusion (tMCAO) and measured real-time PCR to detect miR-34a levels. We demonstrate that the miR-34a levels are elevated in pCECs from tMCAO mice at the time point of BBB opening following 1 h tMCAO and reperfusion. Interestingly, knockout of miR-34a significantly reduces BBB permeability, alleviates disruption of tight junctions, and improves stroke outcomes compared to wild-type (WT) controls. CYC is decreased in the ischemic hemispheres and pCECs from WT but not in miR-34a(−/−) mice following stroke reperfusion. We further confirmed CYC is a target of miR-34a by a dural luciferase reporter gene assay in vitro. Our study provides the first description of miR-34a affecting stroke outcomes and may lead to discovery of new mechanisms and treatments for cerebrovascular and neurodegenerative diseases such as stroke. Nature Publishing Group UK 2020-02-24 /pmc/articles/PMC7040038/ /pubmed/32094435 http://dx.doi.org/10.1038/s41598-020-59997-y Text en © The Author(s) 2020 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hu, Heng
Hone, Emily A.
Provencher, Edward A. P.
Sprowls, Samuel A.
Farooqi, Imran
Corbin, Deborah R.
Sarkar, Saumyendra N.
Hollander, John M.
Lockman, Paul R.
Simpkins, James W.
Ren, Xuefang
MiR-34a Interacts with Cytochrome c and Shapes Stroke Outcomes
title MiR-34a Interacts with Cytochrome c and Shapes Stroke Outcomes
title_full MiR-34a Interacts with Cytochrome c and Shapes Stroke Outcomes
title_fullStr MiR-34a Interacts with Cytochrome c and Shapes Stroke Outcomes
title_full_unstemmed MiR-34a Interacts with Cytochrome c and Shapes Stroke Outcomes
title_short MiR-34a Interacts with Cytochrome c and Shapes Stroke Outcomes
title_sort mir-34a interacts with cytochrome c and shapes stroke outcomes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040038/
https://www.ncbi.nlm.nih.gov/pubmed/32094435
http://dx.doi.org/10.1038/s41598-020-59997-y
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