Title |
Endoplasmic reticulum stress‐mediated upregulation of miR‐29a enhances sensitivity to neuronal apoptosis
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Published in |
European Journal of Neuroscience, February 2016
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DOI | 10.1111/ejn.13160 |
Pubmed ID | |
Authors |
Katie Nolan, Franziska Walter, Liam P Tuffy, Simone Poeschel, Ross Gallagher, Stefan Haunsberger, Isabella Bray, Raymond L Stallings, Caoimhín G Concannon, Jochen H M Prehn |
Abstract |
Disturbance of homeostasis within the ER lumen leads to the accumulation of unfolded and misfolded proteins. This results in the activation of an evolutionary conserved stress response termed ER stress that, if unresolved, induces apoptosis. We previously identified the Bcl-2 homology domain 3 (BH3)-Only Protein Puma as a mediator of ER stress-induced apoptosis in neurons. In the search of alternative contributors to ER stress-induced apoptosis, we noted a downregulation of the anti-apoptotic Bcl-2 family protein Mcl-1 during ER stress in both mouse cortical neurons and human SH-SY5Y neuroblastoma cells. Downregulation of Mcl-1 was associated with an upregulation of microRNA-29a (miR-29a) expression, and subsequent experiments showed that miR-29a targeted the 3' UTR of the anti-apoptotic Bcl-2 family protein, Mcl-1. Inhibition of miR-29a expression using sequence specific antagomirs or the overexpression of Mcl-1 decreased cell death following tunicamycin treatment, while gene silencing of Mcl-1 increased cell death. miR-29a did not alter the signalling branches of the ER stress response, rather its expression was controlled by the ER stress-induced transcription factor activating-transcription-factor-4 (ATF4). Our data demonstrate that the ATF4-mediated upregulation of miR-29a enhances the sensitivity of neurons to ER stress-induced apoptosis. This article is protected by copyright. All rights reserved. |
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Mendeley readers
Geographical breakdown
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Unknown | 33 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 8 | 24% |
Student > Ph. D. Student | 8 | 24% |
Student > Bachelor | 6 | 18% |
Student > Master | 2 | 6% |
Other | 1 | 3% |
Other | 3 | 9% |
Unknown | 5 | 15% |
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Psychology | 1 | 3% |
Other | 3 | 9% |
Unknown | 5 | 15% |