Enhancement of NO release from S-nitrosoalbumin by pollution derived metal ions

Abstract

S-Nitrosothiols act as a comparatively long-lived reservoir of releasable nitric oxide (NO) present in vivo in a variety of body fluids. Soluble constituents of air-borne particulate matter (PM) can affect S-nitrosothiol stability and deregulate NO-based biological signaling. PM aqueous extracts of standard urban dust (SRM 1648a) were prepared, and their effect on human serum S-nitrosoalbumin (HSA–NO) stability was studied. The results indicated that PM extracts induced a release of NO from HSA–NO in a dose-dependent manner. To identify the inorganic components of urban PM responsible for HSA–NO decomposition, the effects of individual metal ions and metal ion mixtures, detected in the SRM 1648a aqueous extract, were examined. The dominant role of copper ions (specifically Cu⁺) was confirmed, but the results did not exclude the influence of other water-soluble PM components. Measurements with the application of several common metal ion chelators confirmed that Cu²⁺ may participate in NO release from HSA–NO and that reduction to monovalent Cu⁺ (responsible for S–NO bond breaking) may occur with the participation of S-nitrosoalbumin. The addition of ascorbic acid (AscA) significantly enhanced the effectiveness of NO release by PM extracts both kinetically and quantitatively, by inducing an increase in the reduction of Cu²⁺ to Cu⁺. These results indicate that AscA present in the respiratory tract lining fluids and plasma may amplify the activity of inorganic components of PM in S-nitrosothiol decomposition.