University Bourgogne Franche-Comté, Faculty of Health Sciences, Dijon, France.
CSGA, Laboratory of taste and olfaction: from the molecule to behavior, University Bourgogne Franche-Comté, INRA, CNRS, France.
PLoS One. 2019 Jul 24;14(7):e0220259. doi: 10.1371/journal.pone.0220259. eCollection 2019.
The olfactory epithelium is continuously exposed to exogenous chemicals, including odorants. During the past decade, the enzymes surrounding the olfactory receptors have been shown to make an important contribution to the process of olfaction. Mammalian xenobiotic metabolizing enzymes, such as cytochrome P450, esterases and glutathione transferases (GSTs), have been shown to participate in odorant clearance from the olfactory receptor environment, consequently contributing to the maintenance of sensitivity toward odorants. GSTs have previously been shown to be involved in numerous physiological processes, including detoxification, steroid hormone biosynthesis, and amino acid catabolism. These enzymes ensure either the capture or the glutathione conjugation of a large number of ligands. Using a multi-technique approach (proteomic, immunocytochemistry and activity assays), our results indicate that GSTs play an important role in the rat olfactory process. First, proteomic analysis demonstrated the presence of different putative odorant metabolizing enzymes, including different GSTs, in the rat nasal mucus. Second, GST expression was investigated in situ in rat olfactory tissues using immunohistochemical methods. Third, the activity of the main GST (GSTM2) odorant was studied with in vitro experiments. Recombinant GSTM2 was used to screen a set of odorants and characterize the nature of its interaction with the odorants. Our results support a significant role of GSTs in the modulation of odorant availability for receptors in the peripheral olfactory process.
嗅上皮组织持续暴露于外源性化学物质,包括气味物质。在过去的十年中,已经证明嗅觉受体周围的酶在嗅觉过程中起着重要作用。已经证明哺乳动物的外源生物代谢酶,如细胞色素 P450、酯酶和谷胱甘肽转移酶(GSTs),参与清除嗅受体环境中的气味物质,从而有助于维持对气味物质的敏感性。GSTs 以前曾被证明参与许多生理过程,包括解毒、类固醇激素生物合成和氨基酸分解代谢。这些酶确保了大量配体的捕获或谷胱甘肽缀合。我们使用多种技术方法(蛋白质组学、免疫细胞化学和活性测定)的结果表明,GST 在大鼠嗅觉过程中起着重要作用。首先,蛋白质组学分析表明,大鼠鼻黏液中存在不同的潜在气味代谢酶,包括不同的 GSTs。其次,使用免疫组织化学方法原位研究了大鼠嗅觉组织中的 GST 表达。第三,使用体外实验研究了主要 GST(GSTM2)气味的活性。使用重组 GSTM2 筛选了一组气味物质,并表征了其与气味物质相互作用的性质。我们的结果支持 GST 在调节外周嗅觉过程中气味物质对受体的可及性方面的重要作用。