This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The vascular pathology of sickle cell disease (SCD) is characterized by altered nitric oxide (NO) metabolism and increased oxidant stress. The etiology of pulmonary hypertension (PH), an increasingly recognized complication of SCD, is, however, unclear and likely multi-factorial. We hypothesize that, in PH of SCD, oxidative stress results in post-translational protein modifications (PTMs) such as tyrosine nitrosylation that contribute to disease pathogenesis. To identify oxidative targets within a high abundance protein, albumin, and lower abundance proteins, we utilized a proteomic approach. Platelet-poor plasma was obtained from 4 age, gender and racially matched subjects in each of the following groups: 1) Sickle cell anemia (Hb-SS) with PH; 2) Hb-SS without PH; 3) Normal hemoglobin controls (Hb-AA) with PH; 4) Hb-AA volunteers without cardiopulmonary disease. Albumin removal cartridges (EMD Biosciences) were used to separate plasma samples into albumin-enriched and albumin-deplete fractions. The degree of plasma separation was confirmed by SDS-PAGE chromatography. Aftercleavage with trypsin, matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) was performed for peptide analysis of the albumin-enriched fractions. Results were correlated with those obtained by liquid chromatography/mass spectroscopy/mass spectrometry (LC/MS/MS). The albumin-deplete fractions were analyzed by two-dimensional protein fractionation (PF2D), followed by MALDI MS.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR010888-10
Application #
7369323
Study Section
Special Emphasis Panel (ZRG1-BECM (03))
Project Start
2006-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
10
Fiscal Year
2006
Total Cost
$667
Indirect Cost
Name
Boston University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Lu, Yanyan; Jiang, Yan; Prokaeva, Tatiana et al. (2017) Oxidative Post-Translational Modifications of an Amyloidogenic Immunoglobulin Light Chain Protein. Int J Mass Spectrom 416:71-79
Sethi, Manveen K; Zaia, Joseph (2017) Extracellular matrix proteomics in schizophrenia and Alzheimer's disease. Anal Bioanal Chem 409:379-394
Hu, Han; Khatri, Kshitij; Zaia, Joseph (2017) Algorithms and design strategies towards automated glycoproteomics analysis. Mass Spectrom Rev 36:475-498
Ji, Yuhuan; Bachschmid, Markus M; Costello, Catherine E et al. (2016) S- to N-Palmitoyl Transfer During Proteomic Sample Preparation. J Am Soc Mass Spectrom 27:677-85
Hu, Han; Khatri, Kshitij; Klein, Joshua et al. (2016) A review of methods for interpretation of glycopeptide tandem mass spectral data. Glycoconj J 33:285-96
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Wang, Yun Hwa Walter; Meyer, Rosana D; Bondzie, Philip A et al. (2016) IGPR-1 Is Required for Endothelial Cell-Cell Adhesion and Barrier Function. J Mol Biol 428:5019-5033
Srinivasan, Srimathi; Chitalia, Vipul; Meyer, Rosana D et al. (2015) Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis. Angiogenesis 18:449-62
Yu, Xiang; Sargaeva, Nadezda P; Thompson, Christopher J et al. (2015) In-Source Decay Characterization of Isoaspartate and ?-Peptides. Int J Mass Spectrom 390:101-109
Steinhorn, Benjamin S; Loscalzo, Joseph; Michel, Thomas (2015) Nitroglycerin and Nitric Oxide--A Rondo of Themes in Cardiovascular Therapeutics. N Engl J Med 373:277-80

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