Barbour Jon, Neuhaus Eva M, Piechura Heike, Stoepel Nadine, Mashukova Anastasia, Brunert Daniela, Sitek Barbara, Stühler Kai, Meyer Helmut E, Hatt Hanns, Warscheid Bettina
Medizinisches Proteom-Center, Ruhr-University Bochum, Universitätsstrasse 150, 44780 Bochum, Germany.
J Proteome Res. 2008 Apr;7(4):1594-605. doi: 10.1021/pr7005796. Epub 2008 Mar 13.
The olfactory system is exposed to a plethora of chemical compounds throughout an organism's lifespan. Anticipation of stimuli and construction of appropriate neural filters present a significant challenge. This may be addressed via modulation of the protein composition of the sensory epithelium in response to environmental conditions. To reveal the mechanisms governing these changes, we employed a comprehensive quantitative proteomics strategy. Two groups of juvenile mice were treated with either pulsed or continuous application of octanal. After 20 days of treatment, we performed a behavioral study and conducted electrophysiological recordings from the olfactory epithelium (OE). Both treated groups demonstrated peripheral desensitization to octanal; however, only the 'continuous' group exhibited habituation. To obtain novel insight into the molecular mechanisms underpinning the peripheral desensitization to octanal, the OE proteomes of octanal-treated mice versus control were quantitatively analyzed using two-dimensional difference gel electrophoresis. We identified several significantly regulated proteins that were functionally classified as calcium-binding proteins, cytoskeletal proteins, and lipocalins. The calcium-binding proteins and cytoskeletal proteins were up-regulated in the 'pulsed' group, whereas in the 'continuous' group, four lipocalins were significantly down-regulated. Uniquely, the lipocalin odorant-binding protein Ia was drastically down-regulated in both groups. The identified proteins reflect changes throughout the entire OE, corresponding to changes in neuronal, non-neuronal, and pericellular processes. We report the regulation of several promising candidates for the investigation of odorant-induced changes of the OE. Among these proteins are different lipocalins, which seem to play a crucial role in the regulation of the sensitivity of the olfactory system.
在生物体的整个生命周期中，嗅觉系统会接触到大量的化合物。对刺激的预期和构建适当的神经过滤器是一项重大挑战。这可以通过响应环境条件调节感觉上皮的蛋白质组成来解决。为了揭示控制这些变化的机制，我们采用了全面的定量蛋白质组学策略。两组幼年小鼠分别接受脉冲式或连续式辛醛处理。处理20天后，我们进行了行为研究，并从嗅觉上皮（OE）进行了电生理记录。两个处理组均表现出对辛醛的外周脱敏；然而，只有“连续”组表现出习惯化。为了深入了解辛醛外周脱敏的分子机制，我们使用二维差异凝胶电泳对辛醛处理小鼠与对照小鼠的OE蛋白质组进行了定量分析。我们鉴定了几种显著调节的蛋白质，其功能分类为钙结合蛋白、细胞骨架蛋白和脂质运载蛋白。钙结合蛋白和细胞骨架蛋白在“脉冲”组中上调，而在“连续”组中，四种脂质运载蛋白显著下调。独特的是，脂质运载蛋白气味结合蛋白Ia在两组中均大幅下调。鉴定出的蛋白质反映了整个OE中的变化，与神经元、非神经元和细胞周围过程的变化相对应。我们报告了几种有前景的候选蛋白的调节情况，用于研究气味剂诱导的OE变化。这些蛋白质中包括不同的脂质运载蛋白，它们似乎在嗅觉系统敏感性的调节中起关键作用。
