Lung proteome alterations in a mouse model for nonallergic asthma

Abstract

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.

Serum ferritin and transferrin levels as serologic markers of methylene diphenyl diisocyanate–induced occupational asthma

“…Gelsolin has been linked to several pathologic conditions, including inflammation, cancer, and amyloidosis 40 ; it is secreted from bronchial epithelial cells and is related to increased mucus production in patients with asthma. 41,42 Finally, multiple annexins were downregulated in the MDI-OA group. Annexins are watersoluble proteins that form voltage-dependent calcium channels within planar lipid bilayers, 43 and they are expressed at reduced levels in asthmatic mice.…”

“…Annexins are watersoluble proteins that form voltage-dependent calcium channels within planar lipid bilayers, 43 and they are expressed at reduced levels in asthmatic mice. 42 Additional studies are needed to evaluate the clinical relevance of each protein for MDI-exposed workers.…”

Group A streptococcus cell‐associated pathogenic proteins as revealed by growth in hyaluronic acid‐enriched media

“…Differentially expressed proteins were selected according to the Wilcoxon two-sample test (p,0.05), i.e. the protein spot must be more intense (or less intense) on at least six gels in each matchset [13].…”

“…The 18 protein spots highlighted in Fig. 1 represent those that were up-or down-regulated according to the Wilcoxon two-sample test [13]. Among the 18 proteins, 12 proteins were up-regulated or were present only on the 2-D gels prepared from cells grown in HA-enriched media and 6 proteins were down-regulated or were absent only on the 2-D gels prepared from cells grown in HA-enriched media.…”

Adduct Formation and Context Factors in Drug Hypersensitivity: Insight from Proteomic Studies

“…In this regard, as for many diseases, proteomics can also be useful in the identification of biomarkers for predisposition to drug or chemical hypersensitivity [22]. Proteomic studies on identification of potential biomarkers have been carried out in animal models, i.e., in mice subjected to hapten challenge [23], and in patients suffering from various types of adverse drug reactions [24]. The importance of proteomics in several aspects of drug toxicity has been the subject of a comprehensive review covering the characterization of the proteome and adductome [25].…”