A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9

摘要: Inappropriate elevation of matrix metalloproteinase-9 (MMP9) is reported to be involved in the pathogenesis chronic obstructive pulmonary disease (COPD). The object this study was identify molecular mechanism underlying increase MMP9 expression, and here we show that oxidative stress-dependent reduction a protein deacetylase, SIRT1, known as putative antiaging enzyme, causes expression. A sirtuin inhibitor, splitomycin, SIRT1 knockdown by RNA interference led an expression human monocytic U937 cells primary sputum macrophages, which detected RT-PCR, Western blot, activity assay, zymography. In fact, level significantly decreased peripheral lungs patients with COPD, inversely correlated promoter activation chromatin immunoprecipitation assay. H(2)O(2) reduced cells; furthermore, cigarette smoke exposure also caused lung tissue A/J mice, concomitant MMP9. Intranasal treatment selective novel small molecule activator, SRT2172, blocked well neutrophilia exercise tolerance. Thus, negative regulator implicated therapeutic approach treating inflammatory diseases, abundant.