Involvement of aldehyde oxidase in the metabolism of aromatic and aliphatic aldehyde-odorants in the mouse olfactory epithelium
Involvement of aldehyde oxidase in the metabolism of aromatic and aliphatic aldehyde-odorants in the mouse olfactory epithelium
复制标题
醛氧化酶参与小鼠嗅上皮芳香族和脂肪族醛气味物质的代谢
DOI：
10.1016/j.abb.2021.109099
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Kotake Y.
中科院分区：
文献类型：
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作者：
Takaoka N;Sanoh S;Ohta S;Esmaeeli M;Leimkuhler S;Kurosaki M;Terao M;Garattini E;Kotake Y.
已知在嗅上皮（OE）中表达的异种代谢酶（XMEs）代谢气味。醛氧化酶（AOX）能识别多种底物，其中包括醛基底物。其中一些AOX底物是气味剂，如苯甲醛和正辛醛。其中一种小鼠AOX亚型，即AOX2 (mAOX2)，被证明在小鼠OE中特异性表达，但其在该组织中代谢气味的作用仍未被探索。在这项研究中，我们研究了小鼠AOX亚型在OE中醛气味剂氧化代谢中的作用。小鼠OE提取物有效地代谢芳香和脂肪醛气味。基因表达分析表明，在OE中不仅表达mAOX2亚型，还表达mAOX3亚型。此外，利用纯化的重组酶对抑制效果进行评估，使我们确定了每种异构体的特异性抑制剂，即氯丙嗪、17β-雌二醇、美萘醌、诺哈曼和雷洛昔芬。利用这些特异性抑制剂，我们确定了mAOX2和mAOX3对小鼠OE中醛类气味剂代谢的贡献。综上所述，这些发现表明mAOX2和mAOX3负责小鼠OE中芳香和脂肪醛气味剂的氧化，这意味着它们参与气味感知。
Xenobiotic-metabolizing enzymes (XMEs) expressed in the olfactory epithelium (OE) are known to metabolize odorants. Aldehyde oxidase (AOX) recognizes a wide range of substrates among which are substrates with aldehyde groups. Some of these AOX substrates are odorants, such as benzaldehyde andn-octanal. One of the mouse AOX isoforms, namely AOX2 (mAOX2), was shown to be specifically expressed in mouse OE but its role to metabolize odorants in this tissue remains unexplored. In this study, we investigated the involvement of mouse AOX isoforms in the oxidative metabolism of aldehyde-odorants in the OE. Mouse OE extracts effectively metabolized aromatic and aliphatic aldehyde-odorants. Gene expression analysis revealed that not only mAOX2 but also the mAOX3 isoform is expressed in the OE. Furthermore, evaluation of inhibitory effects using the purified recombinant enzymes led us to identify specific inhibitors of each isoform, namely chlorpromazine, 17β-estradiol, menadione, norharmane, and raloxifene. Using these specific inhibitors, we defined the contribution of mAOX2 and mAOX3 to the metabolism of aldehyde-odorants in the mouse OE. Taken together, these findings demonstrate that mAOX2 and mAOX3 are responsible for the oxidation of aromatic and aliphatic aldehyde-odorants in the mouse OE, implying their involvement in odor perception.