title: miR-181 targets multiple Bcl-2 family members and influences apoptosis and mitochondrial function in astrocytes.
abstract: Mitochondria are central to the execution of apoptosis, and the Bcl-2 protein family of pro- and anti-apoptotic proteins interacts with mitochondria to regulate apoptosis. Using bioinformatics we predicted that miR-181, a microRNA expressed in brain, could target the 3'UTRs of Bcl-2 family members Bcl-2-L11/Bim, Mcl-1, and Bcl-2. Using the luciferase reporter assay we confirmed these targets. We used mimic and inhibitor to alter miR-181a levels in primary astrocyte cultures and found miR-181a reduction was associated with increased Bcl-2 and Mcl-1 protein levels. Decreased miR-181a levels reduced glucose deprivation induced apoptosis, mitochondrial dysfunction, and loss of mitochondrial membrane potential in astrocytes.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA. ybouyang@stanford.edu
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Ouyang
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
authors.forename: Sibiao
authors.initials: S
authors.lastname: Yue
authors.forename: Rona G
authors.initials: RG
authors.lastname: Giffard
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*
chemical_list: C579094:Mcl1 protein, mouse; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; C529100:mirn181 microRNA, mouse; D008156:Luciferases