Disease relevance of Cyp6a8

• Heterologous expression of the CYP6A2 protein in lepidopteran cells infected with a Cyp6a2-recombinant baculovirus was observed by Western blotting of cell lysates and by spectral characterization of the reduced-CO complex of the P450 [1].

High impact information on Cyp6a8

• To examine whether caffeine, the most widely used xenobiotic compound, would induce insect cytochrome P450 or CYP gene expression, upstream DNA fragments of Cyp6a2 (0.12, 0.26, 0.52 and 0.98-kb) and Cyp6a8 (0.06, 0.1, 0.2, 0.5 and 0.8-kb) genes of Drosophila melanogaster were individually fused to the firefly luciferase (luc) reporter gene [2].
• Endogenous Cyp6a8 and Cyp6a2 genes in these flies also showed caffeine-induced expression [2].
• This suggested that the underproducer strains carry loci which downregulate Cyp6a2 and Cyp6a8 gene expression [3].
• Barbital induces all these genes in all three strains and increases the levels of the two Cyp6a8 transcripts and the 1.8-kb RNA produced by the Cyp6a9 and/or Cyp6a9-related genes [4].
• The polypeptides encoded by these two genes, Cyp6a8 and Cyp6a9, show 77 and 75% amino acid sequence similarity, and 60 and 55% identity with Cyp6a2 of D. melanogaster, respectively [4].

Biological context of Cyp6a8

• These results suggest that -11/-761 Cyp6a8 DNA of the 91-R strain can respond to the active repressor present in the hybrid genome and further support our previous findings that overexpression of Cyp6a8 is a result of mutation of a repressor gene rather than mutation of the cis-regulatory sequences [5].
• Cyp6a8 has two introns of which intron II is similar to the introns of other insect CYP genes with respect to its length and position [5].
• Analysis of Cyp6a8 upstream DNA of the overproducer 91-R strain showed that DNA sequences between -199 and -761 bp are required for the highest constitutive and barbital-induced expression of Cyp6a8 [5].
• In the genome, Cyp6a8 and Cyp6a9 genes are closely clustered within 4 kb and map at region 51C of the second chromosome [4].
• It is also in-frame with the CYP6A8 open reading frame [5].

Associations of Cyp6a8 with chemical compounds

• We show that all three DDT selected P450s can confer resistance to the neonicotinoid imidacloprid but that Cyp6a8 confers no cross-resistance to malathion [6].
• CYP6A8 was produced in Saccharomyces cerevisiae and enzymatically characterized after catalytic activity was reconstituted with D. melanogaster P450 reductase and NADPH [7].
• The Drosophila cytochrome P450 gene Cyp6a2: structure, localization, heterologous expression, and induction by phenobarbital [1].

Other interactions of Cyp6a8

• In between them another Cyp gene is present which is more related to Cyp6a9 than to Cyp6a8 [4].

Analytical, diagnostic and therapeutic context of Cyp6a8

• Induction of two cytochrome P450 genes, Cyp6a2 and Cyp6a8, of Drosophila melanogaster by caffeine in adult flies and in cell culture [2].
• Transformed Drosophila, but not controls, contained CYP6D1 protein as identified by protein immunoblotting, elevated total P450 and elevated CYP6D1 enzymatic activity [8].
• A 1.8 kb cDNA sequence was obtained from 3 overlapping PCR products, with an open reading frame encoding a P450 protein of 516 residues (M(r) 59,182) [9].

References