Presence of splice variant forms of cytochrome P4502D1 in rat brain but not in liver

Chinta, Shankar J. ; Pai, Harish V. ; Ravindranath, Vijayalakshmi (2005) Presence of splice variant forms of cytochrome P4502D1 in rat brain but not in liver Molecular Brain Research, 135 (1-2). pp. 81-92. ISSN 0169-328X

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Cytochromes P450 (P450), a family of heme-containing proteins, is involved in the oxidative metabolism of both foreign and endogenous compounds. Although liver is quantitatively the major organ involved in the metabolism of most xenobiotics, there is increasing evidence that these enzymes are present in extrahepatic tissues, such as lung, kidney, brain, etc and they may contribute to the in situ metabolism of xenobiotics in these organs. The possible relationship between genetic polymorphism seen in P4502D6 and incidence of neurodegenerative diseases, such as Parkinson's disease, has prompted the characterization of P4502D enzymes in rat brain. In the present study, we demonstrate that P4502D1 (the rat homologue of human P4502D6) is constitutively expressed in rat brain and the mRNA and protein are localized predominantly in neuronal cell population in the olfactory bulb, cortex, cerebellum, and hippocampus. An alternate spliced transcript of CYP2D1 having exon 3 deletion was detected in rat brain but not in liver. Deletion of exon 3 causes frame shift and generates a stop codon at 391 bp relative to the start codon ATG leading to premature termination of translation. Thus, Northern blotting and in situ hybridization represent contributions from functional transcripts and alternate spliced variants that do not translate into functional protein. Further, the splice variant having partial inclusion of intron 6 detected in human brain was not detected in rat brain indicating that alternate spliced gene products of P450 enzymes are generated in species-specific and tissue-specific manner.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Brain; Drug Metabolism; Cytochrome P450; CYP2D; Monooxygenase
ID Code:40622
Deposited On:24 May 2011 14:00
Last Modified:17 May 2016 22:38

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