miR-181 targets multiple Bcl-2 family members and influences apoptosis and mitochondrial function in astrocytes |
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Authors: | Ouyang Yi-Bing Lu Yu Yue Sibiao Giffard Rona G |
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Affiliation: | Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA. ybouyang@stanford.edu |
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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. |
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