DJ-1 and its anti-oxidative stress response regulates the expression of sirtuin-1 in COPD epithelial cells

Background: DJ-1 is a multifunctional oxidative stress response protein that protects the cell against reactive oxygen species. DJ-1 binds and activates SIRT1, a NAD+ -dependent Class 3 histone deacetylase, which is down-regulated in COPD patients. Aims: To investigate the effect of oxidative stress on gene/protein expressions and the association of DJ-1 and SIRT1 in COPD patients. Methods: Gene and protein expression of DJ-1 were determined in peripheral lung tissue and BEAS2B cells (human airway epithelial cells) treated with H₂O₂ for 48hr by PCR and Western blotting. To examine whether DJ-1 regulates the expression of SIRT1, BEAS2B cells were transfected with siRNA (DJ-1 and SIRT1). To identify the complex formation between SIRT1 and DJ-1, proteins extracted from BEAS2B cells were immunoprecipitated with DJ-1 antibody. Results: Gene expression of DJ-1 was significantly lower in peripheral lung tissue from COPD patients (n=25, P<0.01) than healthy controls (n=12). Oxidative stress with H<₂O₂ (100µM) significantly reduced DJ-1 at both gene and protein level. Gene and protein expression of SIRT1 was down-regulated in DJ-1 knockdown cells and DJ-1 was also significantly decreased in SIRT1 knockdown cells. DJ-1 was also seen to directly bind SIRT1 in immunoprecipitation experiments. Conclusions: DJ-1 binds and regulates the expression of SIRT1 in epithelial cells. As both DJ-1 and SIRT1 were down-regulated in COPD, the association of these molecules may be a mechanism of impaired anti-ageing and defence against oxidative stress in COPD.