Developmental expression of human microsomal epoxide hydrolase.
Microsomal epoxide hydrolase (mEH) is a critical biotransformation enzyme that catalyzes the hydrolysis of a large number of epoxide intermediates, which arise frequently from the oxidation of pharmaceutical and environmental compounds by the cytochrome P450 mixed function oxygenase system. The enzyme mEH has been implicated directly as a key determinant of certain chemically initiated cancers and developmental toxicities. To evaluate mEH expression in human tissues and provide a framework for assessing the relative risk in the fetus to potential developmental toxins, in the current study, the authors characterized mEH in human tissues as a function of gestational age. Analyses included enzymatic activity determinations, immunochemical quantitation of protein levels and RNA hybridization assays. With respect to activity, hepatic mEH enzymatic levels were strongly correlated with increasing gestational age (r = .82, P < .001). Similarly, mEH activity levels in the liver were highly correlated with protein contents (r = .93, P < .001). However, mEH enzymatic activity in the fetal lung did not exhibit similar concordance nor did measured RNA levels appear to correlate with enzymatic activity levels in fetal or adult tissue samples. Of the fetal tissues surveyed, the liver and adrenal glands exhibited the highest levels of detectable mEH RNA, followed by the lung and kidney. These data suggest that post-transcriptional regulatory pathways may be important in determining constitutive levels of mEH functional activity and that fetuses during early gestation may be uniquely sensitive to the presentation of epoxide-containing xenobiotics compared with fetuses at later stages of development.
Omiecinski
C J
CJ
Department of Environmental Health, University of Washington, Seattle.
Aicher
L
L
Swenson
L
L
D000375:Aging / Q000378:metabolism / Q000502:physiology; D001483:Base Sequence; D005314:Embryonic and Fetal Development / Q000235:genetics; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D008099:Liver / Q000196:embryology / Q000201:enzymology / Q000502:physiology; D008168:Lung / Q000196:embryology / Q000201:enzymology / Q000502:physiology; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D012313:RNA / Q000032:analysis / Q000235:genetics
D012313:RNA; D004851:Epoxide Hydrolases