Gene transcription of the retinoid X receptor alpha (RXRalpha) is regulated by fatty acids and hormones in rat hepatic cells.
This work describes the molecular mechanisms of fatty acid and hormonal modulations of the retinoid X receptor alpha (RXRalpha) in rat liver cells. We examined the effects of different fatty acids (myristic, stearic, oleic, linolenic, and arachidonic acids, EPA, and the peroxisomal proliferator TTA) and several hormones (the glucocorticoid analogue dexamethasone, insulin, and retinoic acid) on the RXRalpha mRNA and protein levels in rat hepatoma cells and cultured hepatocytes. The fatty acids induced the RXRalpha gene expression resulting in up to 3-fold induction. Dexamethasone alone induced the mRNA level and, in combination with fatty acids, an additive or synergistic effect was observed. The dexamethasone-increased mRNA level was obliterated by insulin. The same pattern of regulation of the protein level was observed when determined in cultured hepatocytes, but the induced protein level showed a lower magnitude of stimulation than the mRNA level. This could indicate a post-transcriptional modulation of the RXRalpha gene expression. Time course studies showed a maximal induction of mRNA and protein levels after 18 h and 48 h, respectively. Our results uniformly show that the RXRalpha gene expression is under distinct regulation by fatty acids and hormones which suggests a coupling with the lipid metabolizing system and the hormonal signaling pathway.
Steineger
H H
HH
Institute of Medical Biochemistry, University of Oslo, Blindern, Norway.
Arntsen
B M
BM
Spydevold
O
O
Sørensen
H N
HN
D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D005227:Fatty Acids / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006728:Hormones / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000235:genetics; D047488:Retinoid X Receptors; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology
D005227:Fatty Acids; D006728:Hormones; D007328:Insulin; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin; D003907:Dexamethasone