Lin-Lee Y C, Strobl W, Soyal S, Radosavljevic M, Song M, Gotto A M, Patsch W
Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
J Lipid Res. 1993 Feb;34(2):249-59.
The genes coding for apolipoproteins A-I, C-III, and A-IV are closely linked to one another in the rat genome. Thyroid hormone stimulates apoA-I expression in rat liver by an unusual mechanism that enhances the maturation of mRNA. This hormone also increases apoA-IV mRNA abundance by a mechanism not yet studied, and its role in the expression of apoC-III has not been defined but may be of relevance to the metabolism of triglyceride-rich lipoproteins. We therefore measured the transcriptional activity of the apoA-IV and apoC-III genes and the abundance of their nuclear RNA and total cellular mRNA in livers of control rats and rats made hyper- and hypothyroid. After a single receptor-saturating dose of triiodothyronine (3 mg/100 g body weight), apoA-IV gene transcription increased at 20 min and reached a maximum of 260% of control at 6 h. Increases of transcription were reflected in increases of nuclear and total apoA-IV mRNA levels. ApoC-III gene transcription was temporarily increased to 160% at 2 h without changes in the abundance of its nuclear or total mRNA over 24 h. Lower hormone doses (20-500 micrograms/100 g body weight) stimulated apoA-IV mRNA transcription as well, but tended to reduce transcription from the apoC-III gene. Upon chronic administration of thyroid hormone, apoA-IV transcription decreased to 55% and nuclear apoA-IV RNA levels to 87% of control. However, total cellular apoA-IV mRNA levels increased to 279% of control, implying stabilization of mRNA in the cytoplasm. ApoC-III transcription decreased to 28% of control, but abundance of nuclear and total cellular apoC-III mRNA was reduced to a lesser extent. In hypothyroid rats, apoA-IV gene expression was decreased fourfold at the transcriptional level. In contrast, apoC-III gene transcription increased to 178% of control, but the abundance of nuclear and total cellular apoC-III mRNA did not differ from control rats. Thus, thyroid hormone affects the abundance of apoA-IV mRNA by changing its synthesis and its rate of degradation and enhances the efficiency of apoC-III mRNA maturation, thereby blunting the net effect of altered mRNA synthesis on mRNA abundance.
在大鼠基因组中，编码载脂蛋白A-I、C-III和A-IV的基因彼此紧密相连。甲状腺激素通过一种不同寻常的机制刺激大鼠肝脏中载脂蛋白A-I的表达，该机制可增强mRNA的成熟。这种激素还通过一种尚未研究的机制增加载脂蛋白A-IV mRNA的丰度，其在载脂蛋白C-III表达中的作用尚未明确，但可能与富含甘油三酯的脂蛋白的代谢有关。因此，我们测量了对照大鼠以及甲状腺功能亢进和减退大鼠肝脏中载脂蛋白A-IV和载脂蛋白C-III基因的转录活性及其核RNA和总细胞mRNA的丰度。在给予单次受体饱和剂量的三碘甲状腺原氨酸（3mg/100g体重）后，载脂蛋白A-IV基因转录在20分钟时增加，并在6小时时达到对照的260%的最大值。转录的增加反映在核和总载脂蛋白A-IV mRNA水平的增加上。载脂蛋白C-III基因转录在2小时时暂时增加到160%，但其核或总mRNA的丰度在24小时内没有变化。较低剂量的激素（20 - 500μg/100g体重）也刺激载脂蛋白A-IV mRNA转录，但倾向于降低载脂蛋白C-III基因的转录。长期给予甲状腺激素后，载脂蛋白A-IV转录降至对照的55%，核载脂蛋白A-IV RNA水平降至对照的87%。然而，总细胞载脂蛋白A-IV mRNA水平增加到对照的279%，这意味着细胞质中mRNA的稳定性增加。载脂蛋白C-III转录降至对照的28%，但其核和总细胞载脂蛋白C-III mRNA的丰度降低程度较小。在甲状腺功能减退的大鼠中，载脂蛋白A-IV基因表达在转录水平上降低了四倍。相反，载脂蛋白C-III基因转录增加到对照的178%，但其核和总细胞载脂蛋白C-III mRNA的丰度与对照大鼠没有差异。因此，甲状腺激素通过改变其合成和降解速率来影响载脂蛋白A-IV mRNA的丰度，并提高载脂蛋白C-III mRNA成熟的效率，从而减弱mRNA合成改变对mRNA丰度的净影响。
