Oxidative stress and asthma: proteome analysis of chitinase-like proteins and FIZZ1 in lung tissue and bronchoalveolar lavage fluid.

Oxidative stress and asthma: proteome analysis of chitinase-like proteins and FIZZ1 in lung tissue and bronchoalveolar lavage fluid.
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DOI:
10.1021/pr800685h
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发表时间:
2009-04
影响因子:
4.4
通讯作者:
Loo JA
Loo JA
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang L;Wang M;Kang X;Boontheung P;Li N;Nel AE;Loo JA

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氧化应激在哮喘气道炎症和高反应性的发生发展中起重要作用。卵蛋白(OVA)致敏小鼠肺组织和支气管肺泡灌洗液(BALF)中氧化应激标志物的鉴定可以为了解疾病的发病机制和可能使用抗氧化剂减轻疾病的严重程度提供新的见解。我们使用双向聚丙烯酰胺凝胶电泳法(2D-PAGE)和液质联用法(LC-MS/MS)研究了硫醇抗氧化剂N-乙酰半胱氨酸(NAC)对小鼠OVA模型蛋白质表达的影响。与对照组相比,卵清蛋白攻击组小鼠肺泡灌洗液中至少有6个蛋白或蛋白家族的表达显著增加:几丁质酶3(YM1)、几丁质酶3(YM2)、酸性哺乳动物几丁质酶(AMCase)、肺表面活性物质相关蛋白D(SP-D)、抵抗素样分子α(RELmα)或“在炎症中发现”(FIZZ1),以及结合珠蛋白α亚单位。小鼠哮喘模型肺组织中共有9种蛋白质显著增加,包括YM1、YM2、FIZZ1等与肺重塑相关的蛋白质。Western blotting证实,从OVA攻击小鼠的BAL液和肺组织中测量到YM1/YM2、SP-D和FIZZ1的表达增加。在最后一次OVA激发前,腹腔注射NAC可抑制BALF和肺组织中YM1/YM2、SP-D和FIZZ1的表达。氧化应激蛋白YM1/YM2、FIZZ1和SP-D可能在哮喘的发病机制中发挥重要作用,可能是有用的氧化应激标志物。
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 α (RELMα) or “found in inflammatory 1” (FIZZ1), and haptoglobin α-subunit. A total of 9 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 Ym1/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 Ym1/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.
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