Flavin-containing monooxygenase 5 (FMO 5) (Baeyer-Villiger monooxygenase 1) (EC 1.14.13.-) (hBVMO1) (Dimethylaniline monooxygenase [N-oxide-forming] 5) (EC 22.214.171.124) (Dimethylaniline oxidase 5) (NAPDH oxidase) (EC 126.96.36.199)
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.
- Intestine, Small
- RNA, Messenger
- Reverse Transcriptase Polymerase Chain Reaction
3,3'-Iminodipropionitrile (IDPN) causes degeneration of the olfactory mucosa (OM) in rodents following systemic exposure. Approximately 30% of the OM degenerates in 21-day- and 10-week-old rats following a single 200 or 400 mg/kg intraperitoneal (i.p.) dose of IDPN, whereas 100% olfactory mucosal degeneration occurred in 21-month-old rats. Age-related changes in the flavin-containing monooxygenases (FMOs) or heat shock protein 70 (HSP70) were hypothesized to be responsible for altered olfactory mucosal susceptibility to IDPN. FMO activity in OM was higher than in liver in rats up to 40 weeks of age. Western blots of OM and liver revealed no change in FMO1 protein; however, FMO2, 3, and 5 decreased in olfactory microsomes with age. FMO3 and FMO5 increased in liver microsomes with age. Heat shock protein 70 did not differ between 10-week- and 10-month-old rats in either tissue. The mechanism underlying the increased susceptibility of older rats is likely a complex interaction between the activities of one or more of the enzymes involved in IDPN metabolism in OM and liver.
- Blotting, Western
- HSP70 Heat-Shock Proteins
- Olfactory Mucosa