Author:
Gabr Amir A,Reed Mathew,Newman Donna R,Pohl Jan,Khosla Jody,Sannes Philip L
Abstract
Abstract
Background
Heparin has been shown to modify fundamental biologic processes ranging from blood coagulation and cell proliferation to fibrogenesis and asthma. The goal of this study was to identify specific or broad biologic responses of the rat lung to intratracheal instillation of heparin by targeted proteomic analysis.
Methods
Rats were given either aerosolized 500 μg heparin in 250 μl saline or saline alone. Lungs were harvested at 0, 24, or 96 hours post-treatment and isolated proteins analyzed by two-dimensional gel electrophoresis. Proteins which increased and decreased significantly in treated groups above controls were then selected for identification by mass spectrometry.
Results
Although heparin treatments resulted in a general reduction in cytosolic protein expression, there were significant increases within members of discrete groups of proteins. At 24 hours, proteins which function in cytoskeletal organization and in calcium signaling were up-regulated between 2- and 27-fold above baseline and untreated controls. Increased proteins include annexins V and VI, septin 2, capping G protein, actin-related protein 3, moesin, RhoGDP dissociation inhibitor, and calcyclin. A group of proteins relating to immune response and tumor suppressor function were either up-regulated (tumor suppressor p30/hyaluronic acid binding protein-1, Parkinson disease protein 7, proteosome 28 subunit/interferon-γ inducible protein, and proteosome subunit macropain α-1) or strongly down-regulated (transgelin). At 96 hours, most proteins that had increased at 24 hours remained elevated but to a much lesser degree.
Conclusion
These cumulative observations demonstrate that whole lung heparin treatment results in significant up-regulation of selected groups of proteins, primarily those related to cytoskeletal reorganization and immune function, which may prove to be relevant biomarkers useful in analysis of lung exposures/treatments as well as in system biology studies.
Publisher
Springer Science and Business Media LLC
Reference58 articles.
1. Hanash S: Disease proteomics.
Nature 2003, 422:226–232.
2. Weston AD, Hood L: Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine.
J Proteome Res 2004, 3:179–196.
3. Fehniger TE, Sato-Folatre JG, Malmstrom J, Berglund M, Lindberg C, Brange C, Lindberg H, Marko-Varga G: Exploring the context of the lung proteome within the airway mucosa following allergen challenge.
J Proteome Res 2004, 3:307–320.
4. Li CM, Newman D, Khosla J, Sannes PL: Heparin inhibits DNA synthesis and gene expression in alveolar type II cells.
Am J Respir Cell Mol Biol 2002, 27:345–352.
5. Sannes PL, Khosla J, Cheng PW: Sulfation of extracellular matrices modifies responses of alveolar type II cells to fibroblast growth factors.
Am J Physiol 1996, 271:L688–697.
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