| Retinoic acid isomers applied to human skin in vivo each induce a 4-hydroxylase that inactivates only trans retinoic acid |
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| Author(s): Duell EA, Kang S, Voorhees JJ |
| Source: JOURNAL OF INVESTIGATIVE DERMATOLOGY Volume: 106 Issue: 2 Pages: 316-320 Published: FEB 1996 |
| Times Cited: 34 References: 15 |
| Abstract: Application of all-trans retinoic acid to human skin for 4 d under occlusion produces a marked increase in retinoic acid 4-hydroxylase activity. In this study, the possible induction of other hydroxylases in response to 9-cis and 13-cis retinoic acid applications to adult human skin in vivo was determined. Application of 0.1% all-trans, 0.1% 9-cis, and 0.1% 13-cis retinoic acid to human skin for 2 d resulted in induction of only all-trans retinoic acid 4-hydroxylase activity. The 4-hydroxylase activity in microsomes from the treated tissue ranged from 383 +/- 46 to 531 +/- 59 pg of 4-hydroxy all-trans retinoic acid formed/min/mg protein (n = 6). These same preparations were unable to use 9-cis or 13-cis retinoic acid as substrate for the hydroxylation reaction. Extraction of the retinoic acid isomers from epidermis 48 h after application of 0.1% solution of each isomer yielded significant amounts of all-trans retinoic acid (36-72%) regardless of the isomer applied. The all-trans isomer produced by isomerization of both 9-cis and 13-cis retinoic acids is the likely inducer of the 4-hydroxylase. All-trans retinol and all-trans retinal were unable to compete with all-trans retinoic acid as substrate for 4-hydroxylase enzyme. The 4-hydroxylase induced in response to pharmacological doses of retinoic acids is specific for the all-trans isomer. The inability of 9-cis or 13-cis retinoic acid to induce their own hydroxylation and inactivation or act as substrate for the 4-hydroxylase in skin may have considerable implications in light of the clinical use of retinoids in the treatment of various diseases including cancers. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV MICHIGAN, SCH MED, DEPT DERMATOL, ANN ARBOR, MI USA |
| Publisher: BLACKWELL SCIENCE INC, 238 MAIN ST, CAMBRIDGE, MA 02142 |
| Subject Category: Dermatology |
| IDS Number: TZ567 |
| ISSN: 0022-202X |