NDLI: Cytochrome P4503A: Evidence for mRNA expression and catalytic activity in rat brain

Content Provider	Springer Nature Link
Author	Yadav, Sanjay Dhawan, Alok Seth, Prahlad K. Singh, Ram L. Parmar, Devendra
Copyright Year	2006
Abstract	Studies initiated to investigate the presence of cytochrome P4503A (CYP3A) isoenzymes in brain revealed constitutive mRNA and protein expression of CYP3A1 in rat brain. Western blotting studies showed that pretreatment with CYP3A inducer such as pregnenolone-16α -carbonitrile (PCN) significantly increased the cross reactivity comigrating with hepatic CYP3A1 and CYP3A2 in rat brain microsomes. RT-PCR studies have also shown increase in mRNA expression of CYP3A1 following pretreatment of rats with PCN. The ability of rat brain microsomes to catalyze the demethylation of erythromycin, known to be mediated by CYP3A isoenzymes in liver and significant increase in the activity of erythromycin demethylase (EMD) following pretreatment with dexamethasone or PCN have indicated that CYP3A isoenzymes expressed in brain are functionally active. Kinetic studies revealed that increase in the enzyme activity following pretreatment with PCN resulted in increase in the apparent affinity (Km) and Vmax of the reaction. Similarities in the inhibition of the constitutive and inducible brain and liver EMD activity following in vitro addition of ketoconazole, a inhibitor specific for CYP3A catalysed reactions and anti-CYP3A have further indicated that like in liver, CYP3A isoenzymes catalyse the activity of EMD in rat brain. Data also revealed regional differences in the activity of EMD in the brain. Relatively higher constitutive as well as inducible mRNA expression of CYP3A1 in hypothalamus and hippocampus, the brain regions responsive to steroid hormones have suggested that CYP3A isoenzymes may not only be involved in the process of detoxication mechanism but also in the metabolism of endogenous substrates in brain.
Starting Page	91
Ending Page	99
Page Count	9
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	287
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2006-05-04
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	brain CYP3A enzyme erythromycin RT-PCR western blotting Biochemistry Oncology Medical Biochemistry Cardiology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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