Molecular Genetics and Metabolism Volume 78, Issue 2 , February 2003, Pages 119-135
Nedialka G. Markov (a), A. Pinkas-Sarafov (a), N. Karaman-Jurukovsk (a), V. Jurukovski (1) and M. Simon (2)
From the Living Skin Bank, Department of Oral Biology and Pathology, School of Dental Medicine, SUNY Stony Brook, Stony Brook, NY 11794-8702, USA
Received 10 September 2002; revised 4 December 2002; accepted 5 December 2002; Available online 11 February 2003.
(1) Present address: Department of Cell Biology, NYU Medical Center, 550 First Avenue, MSB650, New York, NY 10016, USA.
(2) Also corresponding author.
Abstract
The biological functions of vitamin A in the epidermis are mediated by all-trans retinoic acid, which is biosynthesized from retinol in two oxidative reactions. The first step involves enzymatic conversion of retinol to retinaldehyde. The physiological significance and relative contributions of the various retinol dehydrogenases to the oxidation of retinol in epidermal cells remain unclear. We report the characterization of a retinol dehydrogenase/reductase of the SDR superfamily, hRoDH-E2, which is abundantly expressed in the epidermis, epidermal appendages and in cultured epidermal keratinocytes. Both in live keratinocytes and in isolated keratinocyte microsomes, where the enzyme normally localizes, hRoDH-E2 functions as a bona fide retinol dehydrogenase. In the prevailing oxidative reaction it recognizes both free- and CRBP-bound retinol, and shows preference toward NADP as a co-substrate. In comparison, hRoDH-E2 retinol dehydrogenase activity in the simple epithelial HEK 293 cells is much lower and in CHO cells is non-existent. hRoDH-E2 transcripts are distributed throughout the epidermal layers but are more abundant in the basal cells. In contrast, the protein is detected predominantly in the basal and the most differentiated living layers. Its synthesis is negatively regulated by retinoic acid. The biochemical properties and the differential expression of hRoDH-E2 in the strata where retinoic acid signaling is critical for epidermal homeostasis support a conclusion that hRoDH-E2 bears the characteristics of the major microsomal retinol dehydrogenase activity in the epidermal keratinocytes in physiological circumstances.
Author Keywords: Retinol dehydrogenase/reductase; Keratinocytes; Retinoid signaling
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