A Review on Current Status and Perspectives of Pituitary Adenoma Nitroproteomics

Oxidative stress is extensively associated with tumorigenesis. A series of studies on stable tyrosine
nitration as a marker of oxidative damage were performed in human pituitaries and adenomas.
Nitrotyrosine sites located within the important protein domains or motifs were involved in the tumor
biological characteristics. This paper reviews published research on the mass spectrometry
characteristics of nitropeptides and nitroproteomics of pituitary controls and adenomas. The
methodology used for nitroproteomics, the current status of human pituitary nitroproteomics studies,
and the future perspectives are reviewed. Enrichment of those low-abundance endogenous
nitroproteins from human tissues or body fluid samples is the first important step for nitroproteomics
studies. Mass spectrometry is the essential approach to determine the amino acid sequence and
locate the nitrotyrosine sites. Bioinformatics analyses, including protein domain and motif analyses,
are needed to locate the nitrotyrosine site within the corresponding protein domains/motifs. Systems
biology techniques, including pathway analysis, are necessary to discover signaling pathway networks
involving nitroproteins from the systematically global point of view. Future quantitative nitroproteomics
will discover pituitary adenoma-specific nitroprotein(s). Structural biology techniques such as X-ray
crystallography analysis will solidly clarify the effects of tyrosine nitration on structure and functions of
a protein. Those studies will eventually address the mechanisms and biological functions of tyrosine
nitration in pituitary tumorigenesis and will discover nitroprotein biomarkers for pituitary adenomas and
targets for drug design for pituitary adenoma therapy. In the future, one needs to perform quantitative
nitroproteomics of each cell type of a pituitary adenoma to discover the nitroprotein biomarker unique
to each cell type of a pituitary adenoma and further analysis of the 3D structure of that nitroprotein. In
addition, it is important to develop quantitative nitroproteomics of body fluids (CSF and
blood plasma) of pituitary adenoma patients to recognize body-fluid nitroproteins or nitropeptide
patterns.