The human pituitary proteome includes all proteins that are expressed in the given time. Unlike a genome, the proteome is not fixed, but it changes depending on the conditions. Proteome science (proteomics) employs a combination of state-of-the-art separation techniques, mass spectrometry, and bioinformatics for the study of proteomes. A promising prospect is the application of proteome research for the investigation of tumor pathologies. Qualitative and quantitative changes in the proteome that are associated with tumor formation can be monitored by a comparison of healthy (control) vs. tumor tissue, and the proteins of interest can be characterized, Here, the proteomics approach will be applied to the study of the proteome in human pituitary macroadenomas (hormonally silent tumors). The objective of the proposed research program is to generate a two-dimensional reference map of human pituitary proteins, and to characterize the proteins whose expression is modified in pituitary macroadenomas. The proteins will be separated by two-dimensional gel electrophoresis, and the 2D maps will be digitized. 2D gel images from control versus tumor proteomes will be compared, and protein spots will be quantified. The proteins whose abundance is altered in pituitary tumors will be identified and characterized. The protein of interest will be digested, and the masses of the resulting peptides will be measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Amino acid sequence of the peptides will be determined by electrospray-ion trap mass spectrometry. Using these peptide-mapping and/or sequencing data, the protein will be identified by searching a protein sequence database. Characterization of differentially expressed pituitary proteins will also include a detailed investigation of changes in posttranslational protein modifications. In addition, a number of prominent proteins from the control pituitary proteome will also be characterized, and a 2D reference database of the human pituitary will be constructed. Knowledge of the changes in protein expression in pituitary macroadenomas will help clarify fundamental mechanisms of macroadenoma formation, which may lead to the development of more effective means to treat and manage these tumors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS042843-05
Application #
7093989
Study Section
Special Emphasis Panel (ZRG1-BMT (01))
Program Officer
Fountain, Jane W
Project Start
2001-06-15
Project End
2007-05-31
Budget Start
2005-06-01
Budget End
2007-05-31
Support Year
5
Fiscal Year
2005
Total Cost
$317,561
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Neurology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Zhan, Xianquan; Wang, Xiaowei; Desiderio, Dominic M (2015) Mass spectrometry analysis of nitrotyrosine-containing proteins. Mass Spectrom Rev 34:423-48
Zhan, Xianquan; Wang, Xiaowei; Desiderio, Dominic M (2013) Pituitary adenoma nitroproteomics: current status and perspectives. Oxid Med Cell Longev 2013:580710
Zhan, Xianquan; Desiderio, Dominic M (2009) Mass spectrometric identification of in vivo nitrotyrosine sites in the human pituitary tumor proteome. Methods Mol Biol 566:137-63
Evans, Chheng-Orn; Moreno, Carlos S; Zhan, Xianquan et al. (2008) Molecular pathogenesis of human prolactinomas identified by gene expression profiling, RT-qPCR, and proteomic analyses. Pituitary 11:231-45
Beranova-Giorgianni, Sarka; Zhao, Yingxin; Desiderio, Dominic M et al. (2006) Phosphoproteomic analysis of the human pituitary. Pituitary 9:109-20
Zhan, Xianquan; Desiderio, Dominic M (2006) Nitroproteins from a human pituitary adenoma tissue discovered with a nitrotyrosine affinity column and tandem mass spectrometry. Anal Biochem 354:279-89
Moreno, Carlos S; Evans, Chheng-Orn; Zhan, Xianquan et al. (2005) Novel molecular signaling and classification of human clinically nonfunctional pituitary adenomas identified by gene expression profiling and proteomic analyses. Cancer Res 65:10214-22
Zhan, Xianquan; Giorgianni, Francesco; Desiderio, Dominic M (2005) Proteomics analysis of growth hormone isoforms in the human pituitary. Proteomics 5:1228-41
Zhan, Xianquan; Desiderio, Dominic M (2005) Comparative proteomics analysis of human pituitary adenomas: current status and future perspectives. Mass Spectrom Rev 24:783-813
Zhao, Yingxin; Giorgianni, Francesco; Desiderio, Dominic M et al. (2005) Toward a global analysis of the human pituitary proteome by multiple gel-based technology. Anal Chem 77:5324-31

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