Retinoic acid is a negative regulator of the neuropeptide Y/peptide YY Y1 receptor gene in SK-N-MC cells.
To identify effectors of neuropeptide Y Y1 receptor gene expression predicted by putative regulatory elements in its 5' flanking region, we examined the effects of several transcriptionally active agents on Y1 receptor mRNA levels and 125I-peptide YY binding capacity in SK-N-MC cells. Phorbol ester caused a rapid, transient 2.6-fold increase in Y1R mRNA levels. However, all trans-retinoic acid caused a rapid, sustained decrease in Y1 receptor mRNA levels (to 25% of control). Cycloheximide pretreatment did not attenuate the maximal inhibitory effect of retinoic acid, but it prolonged the time to achieve maximal efficacy. The retinoic acid effect was secondary to both a significant decrease in Y1 receptor mRNA stability and a decreased Y1 receptor gene transcription rate. Y1 receptor binding capacity was also significantly decreased after retinoic acid treatment (368 +/- 25 vs. 496 +/- 28 fmol/mg of protein for control). These data support a role for retinoic acid as an important agent regulating Y1 receptor gene expression and mediating Y1 receptor down-regulation.
Mannon
P J
PJ
Duke University, Durham, North Carolina, USA.
Kaiser
L M
LM
D001345:Autoradiography; D015152:Blotting, Northern; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D009478:Neuropeptide Y / Q000235:genetics*; D009994:Osmolar Concentration; D019894:Peptide YY; D010455:Peptides / Q000378:metabolism; D014677:Pharmaceutical Vehicles; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D009478:Neuropeptide Y; D010455:Peptides; D014677:Pharmaceutical Vehicles; D012333:RNA, Messenger; D011964:Receptors, Gastrointestinal Hormone; C082172:peptide YY receptor; D019894:Peptide YY; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide