0000000000410056
AUTHOR
Nicolas Thiebaud
Olfactory xenobiotic metabolizing enzymes have an impact on the stimulating properties of some odorants
International audience
Activity and expression of drug metabolizing enzymes in olfactory mucosa of rats treated by hepatic inducers
International audience; Several drug-metabolizing enzymes (DME), such as cytochrome P450- dependent monooxygenases (CYP) and transferases have been characterized in the olfactory epithelium. Some of them are preferentially expressed in this tissue, while others are similar to those present in the liver. The role of these enzymes remains unclear. Since the olfactory mucosa is in direct contact with the external environment, these enzymes can contribute to the detoxification of chemical compounds. In addition, these enzymes could be involved in the olfaction process, especially in the biotransformation of odorants. Indeed, the rapid inactivation and clearance of odorants is a prerequisite for…
Effects of typical inducers on olfactory xenobiotic-metabolizing enzyme, transporter, and transcription factor expression in rats.
International audience; Several xenobiotic-metabolizing enzymes (XMEs) have been identified in the olfactory mucosa (OM) of mammals. However, the molecular mechanisms underlying the regulation of these enzymes have been little explored. In particular, information on the expression of the transcriptional factors in this tissue is quite limited. The aim of the present study was to examine the impact of five typical inducers, Aroclor 1254, 3-methylcholanthrene, dexamethasone, phenobarbital, and ethoxyquin, on the activities and mRNA expression of several XMEs in the OM and in the liver of rats. We also evaluated the effects of these treatments on the mRNA expression of transcription factors an…
Biotransformation of odorants modifies the olfactory signal
International audience
UDP-glucuronosyltransferases (UGTs) in neuro-olfactory tissues: expression, regulation, and function.
International audience; This work aims to review uridine diphosphate (UDP)-glucuronosyltransferase (UGT) expression and activities along different neuronal structures involved in the common physiological process of olfaction: olfactory epithelium, olfactory bulb, and olfactory cortex. For the first time, using high-throughput in situ hybridization data generated by the Allen Brain Atlas (ABA), we present quantitative analysis of spatial distribution of UGT genes in the mouse brain. The olfactory area is a central nervous system site with the highest expression of UGTs, including UGT isoforms not previously identified in the brain. Since there is evidence of the transfer of xenobiotics to th…
Odorant metabolism catalyzed by olfactory mucosal enzymes influences peripheral olfactory responses in rats.
International audience; A large set of xenobiotic-metabolizing enzymes (XMEs), such as the cytochrome P450 monooxygenases (CYPs), esterases and transferases, are highly expressed in mammalian olfactory mucosa (OM). These enzymes are known to catalyze the biotransformation of exogenous compounds to facilitate elimination. However, the functions of these enzymes in the olfactory epithelium are not clearly understood. In addition to protecting against inhaled toxic compounds, these enzymes could also metabolize odorant molecules, and thus modify their stimulating properties or inactivate them. In the present study, we investigated the in vitro biotransformation of odorant molecules in the rat …
Expression and differential localization of xenobiotic transporters in the rat olfactory neuro-epithelium.
International audience; Transporters, such as multidrug resistance P-glycoproteins (MDR), multidrug resistance-related proteins (MRP) and organic anion transporters (OATs), are involved in xenobiotic metabolism, particularly the cellular uptake or efflux of xenobiotics (and endobiotics) or their metabolites. The olfactory epithelium is exposed to both inhaled xenobiotics and those coming from systemic circulation. This tissue has been described as a pathway for xenobiotics to the brain via olfactory perineural space. Thereby, olfactory transporters and xenobiotic metabolizing enzymes, dedicated to the inactivation and the elimination of xenobiotics, have been involved in the toxicological p…
Caractérisation des enzymes du métabolisme des xénobiotiques olfactives chez le rat : régulation et rôle dans la détection périphérique des molécules odorantes
Diplôme : Dr. d'Université; Les enzymes du métabolisme des xénobiotiques (EMX) jouent un rôle central dans la biotransformation et l’élimination de composés étrangers à l’organisme. Organisées en réseau de biotransformation, ces enzymes catalysent des réactions variées (oxydations, conjugaisons …) afin de rendre ces composés plus hydrophiles. Les EMX sont fortement exprimées dans l’épithélium olfactif de mammifères et des études in vitro ont montré qu’elles possèdent des activités élevées. Outre un rôle dans le métabolisme de molécules toxiques, ces enzymes pourraient être impliquées dans la modulation périphérique de l'olfaction. Les EMX pourraient contribuer à maintenir la sensibilité du…