Abstract
Background: Sirtuin-1 (SIRT1), a NAD + -dependent Class III protein deacetylases, known as a putative anti-ageing enzyme, has been shown to be down-regulated in patients with chronic obstructive pulmonary disease (COPD). COPD is characterized by the accelerated ageing of the lung, associated with increased oxidative stress. Both SIRT1 protein and mRNA are reduced in COPD but the mechanisms for this reduction are unknown. Aims: To identify the role of miR-34a, a microRNA previously linked to reduced SIRT1 function, in the regulation of SIRT1 expression in response to oxidative stress. Methods: Protein levels were determined by western blotting and mi/mRNA expression by real-time PCR. Luciferase assays assessed miRNA binding. Results: miR-34a was elevated in peripheral lung samples from patients with COPD (P 2 O 2 (100µM) reduced both SIRT1 mRNA and protein (n=5, P Conclusions: Our results indicate that miR-34a is induced by oxidative stress, suggesting a potential new mechanism by which increased oxidative stress in lungs of COPD patients may reduce SIRT1 expression. Funding: Wellcome trust Programme Grant.
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