Determination of Protein Haptenation by Chemical Sensitizers Within the Complexity of the Human Skin Proteome
Determination of Protein Haptenation by Chemical Sensitizers Within the Complexity of the Human Skin Proteome
复制标题
人类皮肤蛋白质组复杂性中化学敏化剂的蛋白质半抗原测定
作者：
E. Parkinson;Maja Aleksić;R. Cubberley;G. Kaur;J. Vissers;P. Skipp
皮肤致敏与过敏性接触性皮炎的发展相关，通过细胞水平上的一些特定关键事件发生。分子起始事件（MIE）是这些事件序列中的第一个，发生在皮肤暴露于亲电化学物质后，导致皮肤内蛋白质的不可逆半抗原化。该MIE的表征是阐明皮肤致敏不良后果途径的关键步骤，对于为数学模型提供参数以预测化学物质致敏能力至关重要。作为解决这一挑战的第一步，我们将角质细胞细胞系和人类皮肤组织的复杂蛋白裂解物与一系列特性良好的增敏剂进行了暴露，包括二硝基氯苯，5-氯-2-甲基异噻唑-3- 1，肉桂醛和非（或弱）增敏剂6-甲基香豆素。使用一种新的稳定同位素标记方法结合离子迁移辅助数据独立质谱（HDMSE），我们表征了这些致敏剂的半素组。尽管大量高丰度蛋白被半抗原化，但我们也观察到所有3种化学增敏剂都有低丰度蛋白被半抗原化，这表明在复杂的蛋白质背景下，蛋白质丰度并不是驱动半抗原化的唯一决定因素，强调了三级蛋白结构、这些化学增敏剂的氨基酸特异性和增敏剂的效价之间的关系。
Abstract Skin sensitization associated with the development of allergic contact dermatitis occurs via a number of specific key events at the cellular level. The molecular initiating event (MIE), the first in the sequence of these events, occurs after exposure of the skin to an electrophilic chemical, causing the irreversible haptenation of proteins within skin. Characterization of this MIE is a key step in elucidating the skin sensitization adverse outcome pathway and is essential to providing parameters for mathematical models to predict the capacity of a chemical to cause sensitization. As a first step to addressing this challenge, we have exposed complex protein lysates from a keratinocyte cell line and human skin tissue with a range of well characterized sensitizers, including dinitrochlorobenzene, 5-chloro-2-methylisothiazol-3-one, cinnamaldehyde, and the non (or weak) sensitizer 6-methyl coumarin. Using a novel stable isotope labeling approach combined with ion mobility-assisted data independent mass spectrometry (HDMSE), we have characterized the haptenome for these sensitizers. Although a significant proportion of highly abundant proteins were haptenated, we also observed the haptenation of low abundant proteins by all 3 of the chemical sensitizers tested, indicating that within a complex protein background, protein abundance is not the sole determinant driving haptenation, highlighting a relationship to tertiary protein structure and the amino acid specificity of these chemical sensitizers and sensitizer potency.
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影响因子：
4.1
作者：
Cai, Jian;Bhatnagar, Aruni;Pierce, William M., Jr.
通讯作者：
Pierce, William M., Jr.
DOI：
10.1073/pnas.0602816103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Gudiksen, Katherine L.;Gitlin, Irina;Whitesides, George M.
通讯作者：
Whitesides, George M.
影响因子：
7.3
作者：
Jackson PA;Widen JC;Harki DA;Brummond KM
通讯作者：
Brummond KM
影响因子：
3.3
作者：
Spiess, Page C.;Deng, Bin;Hondal, Robert J.;Matthews, Dwight E.;van der Vliet, Albert
通讯作者：
van der Vliet, Albert