Regulation of cytochrome P450 gene expression in the olfactory mucosa.
The mammalian olfactory mucosa (OM) is unique among extrahepatic tissues in having high levels, and tissue-selective forms, of cytochrome P450 (CYP) enzymes. These enzymes may have important toxicological implications, as well as biological functions, in this chemosensory organ. In addition to a tissue-selective, abundant expression of CYP1A2, CYP2A, and CYP2G1, some of the OM CYPs are also known to have an early developmental expression, a resistance to xenobiotic inducers, and a lack of responsiveness to circadian rhythm. Efforts to fully characterize the regulation of CYP expression in the OM, and to identify the underlying mechanisms, are important for our understanding of the physiological functions and toxicological significance of these biotransformation enzymes, and may also shed unique light on the general mechanisms of CYP regulation. The aim of this mini-review is to provide a summary of current knowledge of the various modes of regulation of CYPs expressed in the OM, an update on our mechanistic studies on tissue-selective CYP expression, and a review of the literature on xenobiotic inducibility of OM CYPs. Our goal is to stimulate further studies in this exciting research area, which is of considerable importance, in view of the constant exposure of the human nasal tissues to inhaled, as well as systemically derived, chemicals, the prevalence of olfactory system damage in individuals with neurodegenerative diseases, and the current uncertainty in risk assessments for potential olfactory toxicants.
Ling
Guoyu
G
Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York at Albany, Empire State Plaza, Box 509, Albany, NY 12201-0509, USA.
Gu
Jun
J
Genter
Mary Beth
MB
Zhuo
Xiaoliang
X
Ding
Xinxin
X
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D009831:Olfactory Mucosa / Q000201:enzymology*; D013379:Substrate Specificity; D015262:Xenobiotics / Q000633:toxicity
D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System