Murine CYP2B19 is expressed in a single cell type-differentiated keratinocytes. This novel cytochrome P450 enzyme was cloned, and a full-length cDNA was expressed in E. co/i to produce recombinant CYP2B19. We characterized the activity of the recombinant enzyme and studied biological effects of its metabolites on keratinocytes. CYP2B19 metabolizes arachidonic acid producing epoxyeicosatrienoic (EET) acids, predominantly the 14S,15/?- and 11S, 12/?regioisomers. Unlike other CYP2 epoxygenases, CYP2B19 also produces hydroxyeicosatetraenoic (HETE) acids, mainly the 11S-, 12W-, and 15fl- isomers. This is the first identified mammalian enzyme that produces 12H-HETE, a metabolite associated with epidermal hyperproliferation in humans. In a human keratinocyte cell line, purified EETs produced transient increases in cytosolic free calcium concentrations, depending on the dosage and the specific EET regioisomer used. It is hypothesized that CYP2B19-dependent eicosanoids are involved in intracellular signalling in keratinocytes of cutaneous tissues.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology