Zhang Jun, Cashman John R
Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.
Drug Metab Dispos. 2006 Jan;34(1):19-26. doi: 10.1124/dmd.105.006171. Epub 2005 Sep 23.
The developmentally and tissue-specific expression of flavin-containing monooxygenase (FMO) enzymes has been previously characterized in a number of animal species, including humans, mice, rats, and rabbits. In this study, we used sensitive real-time reverse transcription-polymerase chain reaction methodology to systematically quantify the steady-state mRNA levels of FMO1, 2, 3, 4, and 5 in human tissues. We examined the developmental regulation of these enzymes in brain tissue. FMO1 was found to be down-regulated in human adult brain. The amount of other FMO mRNAs in human brains in different age groups was not significantly different. The study also provided a systematic quantitative comparison of the steady-state mRNA levels of FMO1 to 5 in several major human organs (i.e., liver, lung, kidney, small intestine, and brain). The nature of the quantitative analysis allowed a comprehensive comparison of each FMO mRNA in different tissues as well as among FMO isoforms in the same tissue. A comparison between fetal liver and adult liver showed that FMO1 was the only FMO that was down-regulated; all other FMOs had greater amounts of mRNA in adult liver. FMO5 was the most prominent FMO form detected in fetal liver. The FMO5 mRNA level was nearly as abundant as FMO3 in adult liver. Whereas other FMOs displayed a significant, dominant tissue-specific mRNA profile (i.e., FMO1 in kidney, FMO2 in lung, FMO3 and FMO5 in adult liver), FMO4 mRNA was observed more broadly at relatively comparable levels in liver, kidney, lung, and small intestine.
含黄素单加氧酶(FMO)的发育和组织特异性表达先前已在包括人类、小鼠、大鼠和兔子在内的多种动物物种中得到表征。在本研究中,我们使用灵敏的实时逆转录-聚合酶链反应方法系统地定量了人类组织中FMO1、2、3、4和5的稳态mRNA水平。我们研究了这些酶在脑组织中的发育调控。发现FMO1在人类成脑中下调。不同年龄组人类大脑中其他FMO mRNA的量没有显著差异。该研究还对几种主要人类器官(即肝脏、肺、肾脏、小肠和大脑)中FMO1至5的稳态mRNA水平进行了系统的定量比较。定量分析的性质允许对不同组织中的每种FMO mRNA以及同一组织中的FMO同工型进行全面比较。胎儿肝脏和成人肝脏之间的比较表明,FMO1是唯一下调的FMO;所有其他FMO在成人肝脏中的mRNA量更多。FMO5是在胎儿肝脏中检测到的最主要的FMO形式。FMO5 mRNA水平在成人肝脏中几乎与FMO3一样丰富。虽然其他FMO显示出显著的、占主导地位的组织特异性mRNA谱(即肾脏中的FMO1、肺中的FMO2、成人肝脏中的FMO3和FMO5),但在肝脏、肾脏、肺和小肠中以相对可比的水平更广泛地观察到FMO4 mRNA。