Imperial College London
Alternate

DrJonathanBaker

Faculty of Medicine, National Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 7790jonathan.baker

 
 
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Location

 

223Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Baker:2016:10.1038/srep35871,
author = {Baker, JR and Vuppusetty, C and Colley, T and Papaioannou, AI and Fenwick, P and Donnelly, L and Ito, K and Barnes, PJ},
doi = {10.1038/srep35871},
journal = {Scientific Reports},
title = {Oxidative stress dependent microRNA-34a activation via PI3Kα reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells},
url = {http://dx.doi.org/10.1038/srep35871},
volume = {6},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Sirtuin-1 (SIRT1) and SIRT6, NAD(+)-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress. Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD. Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins. Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction. Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible. Other sirtuin isoforms were not affected by miR-34a. Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases.
AU  - Baker,JR
AU  - Vuppusetty,C
AU  - Colley,T
AU  - Papaioannou,AI
AU  - Fenwick,P
AU  - Donnelly,L
AU  - Ito,K
AU  - Barnes,PJ
DO  - 10.1038/srep35871
PY  - 2016///
SN  - 2045-2322
TI  - Oxidative stress dependent microRNA-34a activation via PI3Kα reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/srep35871
UR  - http://hdl.handle.net/10044/1/41987
VL  - 6
ER  -
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