In this study we developed a quantitative proteomic method named ICATswitch by introducing isotope-coded affinity tag(ICAT)reagents into the biotin-switch method,and used it to investigate S-nitrosation in the liver of normal control C57BL/6J mice and type 2 diabetic KK-Ay mice.We got fifty-eight S-nitrosated peptides with quantitative information in our research,among which thirty-seven had changed S-nitrosation levels in diabetic mouse liver.The S-nitrosated peptides belonged to fortyeight proteins(twenty-eight were new S-nitrosated proteins),some of which were new targets of S-nitrosation and known to be related with diabetes.S-nitrosation patterns were different between diabetic and normal mice.Gene ontology enrichment results suggested that S-nitrosated proteins are more abundant in amino acid metabolic processes.The network constructed for Snitrosated proteins by text-mining technology provided clues about the relationship between S-nitrosation and type 2 diabetes.Our work provides a new approach for quantifying S-nitrosated proteins and suggests that the integrative functions of S-nitrosation may take part in pathophysiological processes of type 2 diabetes.
Nitric oxide (NO) as an immunoregulatory molecule,predominantly depending on S-nitrosylation,acts as a versatile player that executes its regulation and signal transduction for exerting its multi-functions and pleiotropy. Apoptosis of immune cells is an intricate process coupled with positive/negative selection depending on integrated diverse endogenous and exogenous signals and functions to sustain homeostasis in the immune system. Here,the dual roles of NO depending on its concentration in apoptosis are reviewed,breeding up a switch mode in the apoptotic process. Following comments of different switches from apoptosis-death,a new finding of checkpoint (early fluorescence point) of GSNO-initiated thymocyte apoptosis and NOS-GSNOR double control are highlighted. Moreover,S-nitrosylation/denitrosylation,being as a redox switch,logically approaches to networks of metabolism itself and further accesses the neuroendicrine-immune-free radical network as a whole. Moreover,the host defense mediated by NO on pathogens,via protein S-nitrosylation are also discussed.
