Regular ArticleAlternative Splicing of CYP2D mRNA in Human Breast Tissue☆
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DDPH, a novel antihypertensive agent, is a potential dual inhibitor of hepatic CYP2D and CYP3A
2016, Chemico-Biological InteractionsCitation Excerpt :Human CYP2D6 accounts for only roughly 5% of the total content of hepatic CYP, but is known to be responsible for the metabolism of about 20%–25% known drugs including methadone, verapamil and mexiletine [37]. In addition, only one isoform, CYP2D6, is expressed in various tissues in human [38]. The rat and human CYP2D isoforms possess a high sequence identity (>70%), and CYP2D1 is the rat homologue of human CYP2D6 [39].
Investigation of cytochrome P450 inhibitory properties of maslinic acid, a bioactive compound from Olea europaea L., and its structure-activity relationship
2015, PhytomedicineCitation Excerpt :Human CYP2D6 enzyme is involved in the biotransformation of 30% of drugs on the market, although it is expressed at a low level in liver accounting for about 4% of total P450 (Madani et al. 1999). In addition, only one isoform, CYP2D6, is expressed in various tissues including the liver, kidney, placenta, brain, breast, lung and intestine in humans (Huang et al. 1997). The rat and human CYP2D isoforms share a high sequence identity (>70%), and CYP2D1 is the rat ortholog of human CYP2D6 (Venhorst et al. 2003).
Cytochrome P450-catalyzed pathways in human brain: Metabolism meets pharmacology or old drugs with new mechanism of action?
2007, Pharmacology and TherapeuticsCYP2D7 splice variants in human liver and brain: Does CYP2D7 encode functional protein?
2005, Biochemical and Biophysical Research CommunicationsAlternative splicing of vitamin D-24-hydroxylase: A novel mechanism for the regulation of extrarenal 1,25-dihydroxyvitamin D synthesis
2005, Journal of Biological ChemistryCitation Excerpt :The ability of CYP24-SV to suppress synthesis of 1,25-(OH)2D was still evident at saturating doses of substrate. A possible explanation for this is that the splice variant functions in a noncatabolic fashion by competing with 1α-OHase for substrate, although alternative splicing in cytochrome P450 genes has previously been shown to cause changes in function, activity, substrate preference, and tissue specificity (43–46). Our current study is the first example of alternative splicing in CYP24 gene, although Neve et al. (40) have previously reported that deletion of 95 amino acids at the N terminus of the CYP2E1 protein abolished its mitochondrial targeting.
Inter-individual variation of several cytochrome P450 2D6 splice variants in human liver
2005, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Variant b was later suggested to have derived from a pseudogene [14], and sequence alignment suggested that the previously observed variant b is probably CYP2D7P2 or CYP2D8P2. Authentic CYP2D6 transcript with intron 6 retained was subsequently observed in human breast tissue, the MCF-7 cell line, the HepG2 cell line, and normal human lung and lung tumor cells [15–17]. The variant a transcript originally observed in human liver also had the first base in exon 4 deleted; this deletion led to a shift in the reading frame.
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Abbreviations used: CYP, cytochrome P450PCR, polymerase chain reaction; CE, capillary electrophoresis; DIG, digoxygenin; PM, poor metabolizer;
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