Regulation of Stearoyl Coenzyme A Desaturase Expression in Human Retinal Pigment Epithelial Cells by Retinoic Acid

Autor: Stephen M. Prouty, Roshantha A.S. Chandraratna, William Samuel, Barbara Wiggert, Joel S. Gordon, R. Krishnan Kutty, Sahrudaya Nagineni
Rok vydání: 2001
Předmět:
Agonist
medicine.medical_specialty
Carcinoma
Hepatocellular
Tetrahydronaphthalenes
Transcription
Genetic
Receptors
Retinoic Acid
medicine.drug_class
Coenzyme A
Gingiva
Retinoic acid
Antineoplastic Agents
Tretinoin
Retinoid X receptor
Benzoates
Polymerase Chain Reaction
Biochemistry
Gene Expression Regulation
Enzymologic
Cell Line
Retinoids
chemistry.chemical_compound
Internal medicine
Chlorocebus aethiops
Tumor Cells
Cultured
medicine
Animals
Humans
RNA
Messenger
Northern blot
Pigment Epithelium of Eye
Molecular Biology
Alitretinoin
Cells
Cultured
Differential display
Retinoic Acid Receptor alpha
Liver Neoplasms
Retinal
Cell Biology
Blotting
Northern
Molecular biology
Kinetics
Retinoic acid receptor
Retinoid X Receptors
Endocrinology
chemistry
COS Cells
Fatty Acids
Unsaturated
Stearoyl-CoA Desaturase
HeLa Cells
Transcription Factors
Zdroj: Journal of Biological Chemistry. 276:28744-28750
ISSN: 0021-9258
DOI: 10.1074/jbc.m103587200
Popis: Stearoyl-CoA desaturase (SCD) is a regulatory enzyme involved in the synthesis of the monounsaturated fatty acids palmitoleate and oleate. The regulation of SCD is of physiological importance because the ratio of saturated fatty acids to unsaturated fatty acids is thought to modulate membrane fluidity. Differential display analysis of retinal pigment epithelial (ARPE-19) cells identified SCD as a gene regulated by retinoic acid. Two SCD transcripts of 3.9 and 5.2 kilobases in size were found to be expressed in these cells by Northern blot analysis. All-trans-retinoic acid (all-trans-RA) increased SCD mRNA expression in a dose- and time-dependent manner; an approximately 7-fold increase was observed with 1 microm all-trans-RA at 48 h. SCD mRNA expression 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)benzoic acid (TTNPB), a retinoic acid receptor (RAR)-specific agonist. AGN194301, a RAR alpha-specific antagonist, suppressed the SCD expression induced by all-trans-RA, TTNPB, and 9-cis-RA. These results indicate the involvement of RAR alpha in the induction of SCD expression by retinoic acid. However, AGN194204, a RXR (retinoid X receptor) pan agonist, also increased SCD mRNA 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 regulation appears to be mediated through RAR and RXR.
Databáze: OpenAIRE
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