Pituitary Adenoma Nitroproteomics: Current Status and Perspectives

Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China
Oxidative Medicine and Cellular Longevity (Impact Factor: 3.36). 03/2013; 2013:580710. DOI: 10.1155/2013/580710
Source: PubMed

ABSTRACT 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 pituitary and adenoma. 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.

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Available from: Xianquan Zhan, Sep 02, 2014
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    ABSTRACT: Oxidative stress plays important roles in a wide range of diseases such as cancer, inflammatory disease, neurodegenerative disorders, etc. Tyrosine nitration in a protein is a chemically stable oxidative modification, and a marker of oxidative injuries. Mass spectrometry (MS) is a key technique to identify nitrotyrosine-containing proteins and nitrotyrosine sites in endogenous and synthetic nitroproteins and nitropeptides. However, in vivo nitrotyrosine-containing proteins occur with extreme low-abundance to severely challenge the use of MS to identify in vivo nitroproteins and nitrotyrosine sites. A preferential enrichment of nitroproteins and/or nitropeptides is necessary before MS analysis. Current enrichment methods include immuno-affinity techniques, chemical derivation of the nitro group plus target isolations, followed with tandem mass spectrometry analysis. This article reviews the MS techniques and pertinent before-MS enrichment techniques for the identification of nitrotyrosine-containing proteins. This article reviews future trends in the field of nitroproteomics, including quantitative nitroproteomics, systems biological networks of nitroproteins, and structural biology study of tyrosine nitration to completely clarify the biological functions of tyrosine nitration. © 2013 Wiley Periodicals, Inc. Mass Spec Rev.
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    ABSTRACT: Background Clinically nonfunctional pituitary adenomas (NFPAs) without any clinical evaluation of hormone and with a difficulty in its early-stage diagnosis are highly heterogeneous with different hormone expressions in NFPA tissues, including luteinizing hormone (LH)-positive, follicle-stimulating hormone (FSH)-positive, LH/FSH-positive, and negative (NF). Elucidation of molecular mechanisms and discovery of biomarkers common and specific to those different subtypes of NFPAs will benefit NFPA patients in early-stage diagnosis and individualized treatment.Methods Two-dimensional gel electrophoresis (2DGE) and PDQuest image analyses were used to compare proteomes of different subtypes of NFPAs (NF-, LH-, FSH-, and LH/FSH-positive) relative to control pituitaries (Con). Differentially expressed proteins (DEPs) were characterized with mass spectrometry (MS). Each set of DEPs in four subtypes of NFPAs was evaluated with overlap analysis and signaling pathway network analysis with comparison to determine any DEP and pathway network that are common and specific to each subtype of NFPA.ResultsA total of 93 differential protein-spots were determined with comparison of each NFPA type (NF-, LH-, FSH-, and LH/FSH-positive) versus control pituitaries. A total of 76 protein-spots were MS-identified (59 DEPs in NF vs. Con; 65 DEPs in LH vs. Con; 63 DEPs in FSH vs. Con; and 55 DEPs in LH/FSH vs. Con). A set of DEPs and pathway network data were common and specific to each NFPA subtype. Four important common pathway systems included MAPK-signaling abnormality, oxidative stress, mitochondrial dysfunction, and cell-cycle dysregulation. However, these pathway systems were, in fact, different among four types of NFPAs with different protein-expression levels of most of nodes, different protein profiles, and different pathway network profiles.Conclusions These result data demonstrate that common and specific DEPs and pathway networks exist in four NFPA subtypes, and clarify proteome heterogeneity of four NFPA subtypes. Those findings will help to elucidate molecular mechanisms of NFPAs, and discover protein biomarkers to effectively manage NFPA patients towards personalized medicine.
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