Mass spectrometry analysis of S-nitrosylation of proteins and its role in cancer, cardiovascular and neurodegenerative diseases

Mass spectrometry (MS) has become an indispensable tool in the study of protein identification, protein interactions, and post-translational modifications (PTMs). S-nitrosylation is a major nitric oxide-dependent covalent PTM that targets specific cysteine residues and affects a variety of processes in diverse biological systems. Nowadays, the significance of protein S-nitrosylation in cellular physiology and pathophysiology is increasingly recognized. To deeply understand the formation, selectivity, and regulatory roles of S-nitrosylation, global identifications of S-nitrosylated proteins and their modification sites are highly required. This review summarizes the currently available approaches combining with MS for the analysis of protein S-nitrosylation. Sample preparation techniques specific to S-nitrosylated proteins are evaluated. Meanwhile, we also demonstrate the MS-based qualitative and quantitative proteomic strategies for S-nitrosylation measurement. Roles of protein S-nitrosylation in human diseases are further discussed with emphasis on cancer, cardiovascular and neurodegenerative diseases. In the end, current limitations and future research directions are presented. (c) 2022 Elsevier B.V. All rights reserved.