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- Title
Oxidation of 7-Ethoxycoumarin and Conjugation of Umbelliferone by Intact, Viable Epidermal Cells from the Hairless Mouse.
- Authors
Coomes, Marguerite Wilton; Sparks, Rebecca W.; Fouts, James R.
- Abstract
Intact, viable (>80%) epidermal cells were isolated from the hairless mouse. These cells metabolized 7-ethoxycoumarin (7-EC) to umbelliferone (UMB) (3 pmol/min/106 cells) and UMB to the sulfate and glucuronide conjugates (1 pmol/min/106 cells). The rate of oxidation in intact cells compared well with that in disrupted cells with added NADPH, but conjugation proceeded more rapidly in disrupted cells with added cofactors, due to a combination of "activation" of the UDP-glucuronosyltransferase, and to a limitation of activity by the concentration of UDP-glucuronic acid in the intact cells. Pretreatment of the animals with 5,6-benzoflavone resulted in a 5-fold increase in the rate of oxidation, and a 2-fold increase in both the rate of conjugation and the intracellular concentration of UDP-glucuronic acid. UDP-glucuronic acid concentration in isolated cells increased during incubation with glucose, and was regenerated to a steady-state concentration on incubation of cells with UMB. Pretreatment of animals with 5,6-benzoflavone decreased the percentage of metabolite conjugated (from 30% to 15%), whereas adding an inhibitor of oxidation, ellipticine, to cells isolated from pretreated animals, increased the percentage of metabolite conjugated (from 15% to 40%). Sulfation of UMB was almost undetectable, except at very low concentrations (<10 nm) of substrate. Thus, glucuronidation of UMB in epidermal cells may be limited by UDP-glucuronic acid availability; sulfation in the epidermis may contribute little to the conjugation of UMB; and >70% of the products of 7-EC oxidation in the skin may remain unconjugated.
- Subjects
CELLS; EPIDERMIS; LABORATORY mice; GLUCOSE; OXIDATION; EPITHELIUM; CHEMICAL inhibitors; SKIN
- Publication
Journal of Investigative Dermatology, 1984, Vol 82, Issue 6, p598
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12261390