title: Oxidative stress and asthma: proteome analysis of chitinase-like proteins and FIZZ1 in lung tissue and bronchoalveolar lavage fluid.
abstract: 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 (Yml), Chitinase 3-like protein 4 (Ym2), acidic mammalian Chitinase (AMCase), pulmonary surfactant-associated protein D (SP-D), resistin-like molecule alpha (RELMalpha) 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 Yml, Ym2, FIZZ1, and other lung remodeling-related proteins. Western blotting confirmed increased Yml/Ym2, 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 Yml/Ym2, 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.
authors.affiliation: Division of NanoMedicine, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.forename: Meiying
authors.initials: M
authors.lastname: Wang
authors.forename: Xuedong
authors.initials: X
authors.lastname: Kang
authors.forename: Pinmanee
authors.initials: P
authors.lastname: Boontheung
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Andre E
authors.initials: AE
authors.lastname: Nel
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Loo
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002688:Chitinases / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000502:physiology*; D020543:Proteome / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D020543:Proteome; C413576:Retnla protein, mouse; D002688:Chitinases; D000111:Acetylcysteine