Zhang Xiuling, Zhang Qing-Yu, Liu Dazhi, Su Ting, Weng Yan, Ling Guoyu, Chen Ying, Gu Jun, Schilling Boris, Ding Xinxin
Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12201-0509, USA.
Drug Metab Dispos. 2005 Oct;33(10):1423-8. doi: 10.1124/dmd.105.005769. Epub 2005 Jul 13.
Despite recent progress in the identification and characterization of numerous nasal biotransformation enzymes in laboratory animals, the expression of biotransformation genes in human nasal mucosa remains difficult to study. Given the potential role of nasal biotransformation enzymes in the metabolism of airborne chemicals, including fragrance compounds and therapeutic agents, as well as the potential interspecies differences between laboratory animals and humans, it would be highly desirable to identify those biotransformation genes that are expressed in human nasal mucosa. In this study, a global gene expression analysis was performed to compare biotransformation enzymes expressed in human fetal and adult nasal mucosa to those expressed in liver. The identities of a list of biotransformation genes with apparently nasal mucosa-selective expression were subsequently confirmed by RNA-polymerase chain reaction (PCR) and DNA sequencing of the PCR products. Further quantitative RNA-PCR experiments indicated that, in the fetus, aldehyde dehydrogenase 6 (ALDH6), CYP1B1, CYP2F1, CYP4B1, and UDP glucuronosyltransferase 2A1 are expressed preferentially in the nasal mucosa and that ALDH7, flavin-containing monooxygenase 1, and glutathione S-transferase P1 are at least as abundant in the nasal mucosa as in the liver. The nasal mucosal expression of CYP2E1 was also detected. These findings provide a basis for further explorations of the metabolic capacity of the human nasal mucosa for xenobiotic compounds.
尽管近期在实验动物中对多种鼻生物转化酶的鉴定和特性研究取得了进展，但人类鼻黏膜中生物转化基因的表达仍难以研究。鉴于鼻生物转化酶在空气中化学物质（包括香料化合物和治疗剂）代谢中的潜在作用，以及实验动物和人类之间可能存在的种间差异，确定那些在人类鼻黏膜中表达的生物转化基因将非常有必要。在本研究中，进行了一项全局基因表达分析，以比较人类胎儿和成人鼻黏膜中表达的生物转化酶与肝脏中表达的生物转化酶。随后通过RNA聚合酶链反应（PCR）和PCR产物的DNA测序，证实了一系列具有明显鼻黏膜选择性表达的生物转化基因的身份。进一步的定量RNA-PCR实验表明，在胎儿中，醛脱氢酶6（ALDH6）、细胞色素P450 1B1（CYP1B1）、细胞色素P450 2F1（CYP2F1）、细胞色素P450 4B1（CYP4B1）和尿苷二磷酸葡萄糖醛酸基转移酶2A1（UDP glucuronosyltransferase 2A1）在鼻黏膜中优先表达，并且醛脱氢酶7（ALDH7）、含黄素单加氧酶1和谷胱甘肽S-转移酶P1在鼻黏膜中的丰度至少与肝脏中的一样高。还检测到了细胞色素P450 2E1（CYP2E1）在鼻黏膜中的表达。这些发现为进一步探索人类鼻黏膜对外源化合物的代谢能力提供了基础。
