Lung proteome alterations in a mouse model for nonallergic asthma.
A mouse model for nonatopic asthma was employed to study the alterations of the lung proteome to gain insight into the underlying molecular mechanisms of disease pathophysiology post-challenge. Lung samples from asthmatic and control mice were used to generate 24 high quality two-dimensional electrophoresis gels wherein 2115 proteins were examined for disease relevance. In total, 23 proteins were significantly up- or down-regulated following hapten-challenge of dinitro-fluorobenzene-hypersensitive mice. Twenty proteins were identified by mass spectrometry, of which 18 could be linked to asthma related symptoms, such as stress and inflammation, lung detoxification, plasma exudation and/or tissue remodeling. As such, proteomics was clearly vindicated as a means of studying this complex disease phenomenon. The proteins found in this study may not necessarily play a role in the immunological mechanisms and/or pathophysiology of asthma development. However, they may prove useful as surrogate biomarkers for quantitatively monitoring disease state progression or response to therapy. The mathematics of achieving statistical confidence from low numbers of gel replicates containing large numbers of independent variables stress the need for high numbers of replicates to better sample the population of proteins revealed by two-dimensional gel electrophoresis.
Houtman
René
R
Department of Pharmaceutical Proteomics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands. r.houtmann@pharm.uu.nl
Krijgsveld
Jeroen
J
Kool
Mirjam
M
Romijn
Edwin P
EP
Redegeld
Frank A
FA
Nijkamp
Frans P
FP
Heck
Albert J R
AJ
Humphery-Smith
Ian
I
D000199:Actins / Q000032:analysis; D000429:Alcohol Oxidoreductases / Q000032:analysis; D000818:Animals; D017317:Annexin A6 / Q000032:analysis; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D001557:Benzenesulfonates / Q000276:immunology / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004139:Dinitrofluorobenzene / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D008401:Gas Chromatography-Mass Spectrometry; D018260:Gelsolin / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D006360:Heat-Shock Proteins / Q000032:analysis; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D007525:Isoelectric Focusing; D008168:Lung / Q000737:chemistry* / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins / Q000032:analysis; D011506:Proteins / Q000032:analysis; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D012709:Serum Albumin / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016608:Talin / Q000032:analysis; D016596:Vinculin / Q000032:analysis
D000199:Actins; D017317:Annexin A6; D001557:Benzenesulfonates; D018260:Gelsolin; D006360:Heat-Shock Proteins; C489275:Hint1 protein, mouse; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D020543:Proteome; D012709:Serum Albumin; D016608:Talin; C007488:dinitrobenzenesulfonic acid; D016596:Vinculin; C072061:coronin proteins; D004139:Dinitrofluorobenzene; D000429:Alcohol Oxidoreductases; D005982:Glutathione Transferase