OLN-93 oligodendrocytes synthesize all-trans-retinoic acid in vitro

After traumatic injury to the central nervous system (CNS), various cytokin es orchestrate the physiological responses of injured neurons and glial cel ls. The control of these intercellular signals is of major interest from a medical point of view. Since the transcriptional activator retinoic acid (R A) is known to regulate gene expression of cytokines in various cell cultur e systems we investigated the role of RA signaling in glial cells. The tran scriptional activity of RA-induced genes is largely determined by the distr ibution of RA, which in turn depends on the local oxidation of retinaldehyd e (RAL). This is synthesized from retinol or internalized as a component of vitamin A. Using high-pressure liquid chromatography and an RA-sensitive r eporter cell line, we showed that OLN-93 cells, which serve as a model syst em for CNS oligodendrocytes, convert all-trans-RAL to the biologically acti ve form all-trans-RA, but neither oxidize 9-cis-RAL nor isomerize RA enzyma tically. The oligodendrocyte cell line expresses a cytosolic aldehyde dehyd rogenase with an apparent molecular weight of 54-57 kDa and pi of 5.3-5.7. As indicated by a zymography bioassay, this enzyme is responsible for RA sy nthesis. The reaction requires NAD+ as cosubstrate and can be inhibited by disulfiram and citral. No other RA-producing enzyme activities were detecte d. These findings are in accordance with a putative role for retinoid signa ling in neuroglial interactions in the CNS.