Regulation of stearoyl coenzyme a desaturase expression in human retinal pigment epithelial cells by retinoic acid

Stearoyl-CoA desaturase (SCD) is a regulatory enzyme involved in the synthe sis of the monounsaturated fatty acids palmitoleate and oleate. The regulat ion of SCD is of physiological importance because the ratio of saturated fa tty acids to unsaturated fatty acids is thought to modulate membrane fluidi ty. Differential display analysis of retinal pigment epithelial (ARPE-19) c ells identified SCD as a gene regulated by retinoic acid. Two SCD transcrip ts of 3.9 and 5.2 kilobases in size were found to be expressed in these cel ls by Northern blot analysis. All-trans-retinoic acid (all-trans-RA) increa sed SCD mRNA expression in a dose- and time-dependent manner; a similar to7 -fold increase was observed with 1 mum all-trans-RA at 48 h. SCD m-RNA expr ession was also increased by 9-cis-retinoic acid (9-cis-RA) as well as 4-(E -2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzo ic acid (TT-NPB), a retinoic acid receptor (RAR)-specific agonist. AGN19430 1, a RAR alpha -specific antagonist, suppressed the SCD expression induced by all-trans-RA, TTNPB, and 9-cis-RA. These results indicate the involvemen t of RAR alpha in the induction of SCD expression by retinoic acid. However , AGN194204, a RXR (retinoid X receptor) pan agonist, also increased SCD mR NA expression. This increase was not blocked by AGN194301, suggesting that an RAR-independent mechanism may also be involved. Thus, SCD expression in retinal pigment epithelial cells is regulated by retinoic acid, and the reg ulation appears to be mediated through RAR and RXR.