THYROID-HORMONE MODULATES APOLIPOPROTEIN-A-I GENE-EXPRESSION AT THE POSTTRANSCRIPTIONAL LEVEL IN HEP G2 CELLS

Hyperthyroidism is associated with elevated plasma levels of apolipoprotein Al (ape AI). We have examined the effects of 3,3',-5-triiodothyronine on apo Al mRNA, transcription run-on activity, apo AI mRNA half-life, and the rate of protein synthesis in Hep G2 cells, to understand the molecular mechanism by which thyroid hormone regulates apo Al gene expression. Incubation with thyroid hormone increased the apo AI and apo All mRNA concentrations twofold. Cycloheximide alone caused a significant increase in apo Al mRNA. Nuclear run-on assays indicate that thyroid hormone did not change the rate of the apo Al gene transcription at 6, 12 or 24 h, showing that thyroid hormone did not modulate apo Al gene transcription. Kinetic studies performed in the presence of actinomycin D showed that the half-lift of apo AI mRNA was increased 2-3-fold by thyroid hormone over control cells. Thyroid hormone did not change the incorporation of [S-35]methionine into immunoprecipitable apo AI. Pulse-chase experiments demonstrated that there was no change in the secretion and degradation rates of labeled apo Al in response to T3. This suggests that thyroid hormone does not affect the catabolism of apo Al (degradation or/and uptake) and that translation control strongly influences the regulation of apo Al gene expression. The stabilization of apo Al mRNA by thyroid hormone and its role in translation remain to be elucidated.