期刊
JOURNAL OF PROTEOME RESEARCH
卷 8, 期 4, 页码 1631-1638出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr800685h
关键词
proteomics; asthma pathogensis; N-acetylcysteine; antioxidant; diesel exhaust particle; oxidative stress
资金
- United States Public Health service [1101 ES012053, 1101 ES013432]
- UCLA AADCRC [U19 AI070453]
- W. M. Keck Foundation
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U19AI070453] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES012053, R01ES013432] Funding Source: NIH RePORTER
Oxidative stress plays an important role in the development of airway inflammation and hyperreactivity in asthma. The identification of oxidative stress markers in bronchoalveolar lavage fluid (BALF) and lung tissue from ovalbumin (OVA) sensitized mice could provide new insight into disease pathogenesis and possible use of antioxidants to alleviate disease severity. We used two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the impact of the thiol antioxidant, N-acetylcysteine (NAC), on protein expression in a murine OVA model. At least six proteins or protein families were found to be significantly increased in BALF from OVA-challenged mice compared to a control group: Chitinase 3-like protein 3 (Ym1), Chitinase 3-like protein 4 (Ym2), acidic mammalian Chitinase (AMCase), pulmonary surfactant-associated protein D (SP-D), resistin-like molecule a (RELM alpha) or found in inflammatory 1 (FIZZ1), and haptoglobin alpha-subunit. A total of nine proteins were significantly increased in lung tissue from the murine asthma model, including Ym1, Ym2, FIZZ1, and other lung remodeling-related proteins. Western blotting confirmed increased YmlNm2, SP-D, and FIZZ1 expression measured from BAL fluid and lung tissue from OVA-challenged mice. Intraperitoneal NAC administration prior to the final OVA challenge inhibited YmlNm2, SP-D, and FIZZ1 expression in BALF and lung tissue. The oxidative stress proteins, Ym1/Ym2, FIZZ1, and SP-D, could play an important role in the pathogenesis of asthma and may be useful oxidative stress markers.
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