Modification of the response of olfactory receptors to acetophenone by CYP1a2.
Modification of the response of olfactory receptors to acetophenone by CYP1a2.
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DOI：
10.1038/s41598-017-10862-5
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发表时间：
2017-08-31
影响因子：
4.6
通讯作者：
Yohda M
中科院分区：
文献类型：
--
作者：
Asakawa M;Fukutani Y;Savangsuksa A;Noguchi K;Matsunami H;Yohda M
嗅觉是通过气味分子与嗅觉受体(ORs)的结合来调节的。鼻腔粘液中含有大量蛋白质，它们通过不同的机制促进嗅觉。细胞色素P450(CYP)家族成员存在于嗅觉上皮细胞中，并被认为通过气味分子的酶转化来影响嗅觉。在这项研究中，我们研究了Cyps对异种细胞中ORs的配体反应的影响。在所测试的细胞色素P450中，共表达的细胞色素P1A2显著影响包括MOR161-2在内的多种受体对苯乙酮的反应。在表达细胞色素P1A2的细胞上观察到苯乙酮转化为水杨酸甲酯。表达MOR161-2的细胞对水杨酸甲酯的反应明显大于对苯乙酮的反应。最后，我们以磷酸化的核糖体蛋白S6为标记物，分析了体内表达MOR161-2的嗅神经元的反应。MOR161-2在体内对苯乙酮和水杨酸甲酯均有反应。用PBS冲洗小鼠鼻腔后，MOR161-2对苯乙酮的反应减弱，而对水杨酸甲酯的反应不变。我们的数据表明，CYP1A2通过将苯乙酮转化为水杨酸甲酯来影响OR的激活。
Olfaction is mediated by the binding of odorant molecules to olfactory receptors (ORs). There are numerous proteins in the nasal mucus, and they contribute to olfaction through various mechanisms. Cytochrome P450 (CYP) family members are known to be present in the olfactory epithelium and are thought to affect olfaction by enzymatic conversion of odorant molecules. In this study, we examined the effects of CYPs on the ligand responses of ORs in heterologous cells. Among the CYPs tested, co-expression of CYP1a2 significantly affected the responses of various ORs, including MOR161-2, to acetophenone. Conversion of acetophenone to methyl salicylate was observed in the medium of CYP1a2-expressing cells. MOR161-2-expressing cells exhibited significantly greater responses to methyl salicylate than to acetophenone. Finally, we analyzed the responses of olfactory neurons expressing MOR161-2 in vivo using the phosphorylated ribosomal protein S6 as a marker. MOR161-2 responded to both acetophenone and methyl salicylate in vivo. When the olfactory mucus was washed out by the injection of PBS to mouse nasal cavity, the response of MOR161-2 to acetophenone was reduced, while that to methyl salicylate did not change. Our data suggest that CYP1a2 affects OR activation by converting acetophenone to methyl salicylate.
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影响因子：
3.4
作者：
Mayer, Ulrich;Kueller, Alexander;Moehrlen, Frank
通讯作者：
Moehrlen, Frank
影响因子：
64.5
作者：
Saito, H;Kubota, M;Matsunami, H
通讯作者：
Matsunami, H
影响因子：
64.5
作者：
Malnic, B;Hirono, J;Buck, LB
通讯作者：
Buck, LB
DOI：
10.1083/jcb.201008163
发表时间：
2010-11-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
DeMaria S;Ngai J
通讯作者：
Ngai J
影响因子：
3.8
作者：
Gu, J;Su, T;Ding, XX
通讯作者：
Ding, XX