Mechanisms of biological S-nitrosation and its measurement

Abstract

Nitric oxide (NO) exhibits multiple biological actions through formation of various oxidized intermediates derived from NO. Among them, nitrosothiol adducts (RS-NOs) with the sulfhydryl moiety of proteins and amino acids appears to be an important species in view of its unique chemical reactivity. Understanding of the biologically relevant S-nitrosation mechanism is essential because RS-NOs seem to be critically involved in modulation of intracellular and intercellular signal transduction, including gene transcription, cell apoptosis, and oxidative stress. RS-NOs have been recently found to be formed efficiently via one-electron oxidation of NO catalyzed by ceruloplasmin, a major copper-containing protein in mammalian plasma. Ceruloplasmin is synthesized mainly by hepatocytes, but it is also expressed by other cells such as macrophages and astrocytes. Once RS-NOs are formed, they function as NO transporters in biological systems, the NO being transferred to different sulfhydryls of various biomolecules. This transfer may be mediated by transnitrosation reactions occurring chemically or enzymatically by a means of specific enzymes such as protein disulfide isomerase. The molecular mechanism of biological S-nitrosation is discussed as related to the important physiological and pathophysiological functions of RS-NOs. Also, RS-NO assays that are being successfully used for detection of biological S-nitrosation are briefly reviewed.