title: MiR-34a regulates blood-brain barrier permeability and mitochondrial function by targeting cytochrome c.
abstract: The blood-brain barrier is composed of cerebrovascular endothelial cells and tight junctions, and maintaining its integrity is crucial for the homeostasis of the neuronal environment. Recently, we discovered that mitochondria play a critical role in maintaining blood-brain barrier integrity. We report for the first time a novel mechanism underlying blood-brain barrier integrity: miR-34a mediated regulation of blood-brain barrier through a mitochondrial mechanism. Bioinformatics analysis suggests miR-34a targets several mitochondria-associated gene candidates. We demonstrated that miR-34a triggers the breakdown of blood-brain barrier in cerebrovascular endothelial cell monolayer in vitro, paralleled by reduction of mitochondrial oxidative phosphorylation and adenosine triphosphate production, and decreased cytochrome c levels.
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Mimi
authors.initials: M
authors.lastname: Bukeirat
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Saumyendra N
authors.initials: SN
authors.lastname: Sarkar
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia, USA Experimental Stroke Core, Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Dominic D
authors.initials: DD
authors.lastname: Quintana
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia, USA Experimental Stroke Core, Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia, USA Experimental Stroke Core, Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, West Virginia, USA xuren@hsc.wvu.edu.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Ren
mesh_terms: D000244:Adenosine Diphosphate / Q000096:biosynthesis; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000235:genetics / Q000502:physiology; D019295:Computational Biology; D045304:Cytochromes c / Q000235:genetics* / Q000502:physiology*; D042783:Endothelial Cells; D004730:Endothelium, Vascular / Q000166:cytology; D007700:Kinetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics* / Q000502:physiology*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000502:physiology; D010539:Permeability; D019108:Tight Junctions
chemical_list: C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D000244:Adenosine Diphosphate; D045304:Cytochromes c
keywords: Blood–brain barrier; cerebrovascular endothelial cells; cytochrome c; mir-34a; mitochondria