Hu L, Gudas L J
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts.
Mol Cell Biol. 1990 Jan;10(1):391-6. doi: 10.1128/mcb.10.1.391-396.1990.
Retinoic acid (RA) receptor alpha (RAR alpha) and RAR gamma steady-state mRNA levels remained relatively constant over time after the addition of RA to F9 teratocarcinoma stem cells. In contrast, the steady-state RAR beta mRNA level started to increase within 12 h after the addition of RA and reached a 20-fold-higher level by 48 h. This RA-associated RAR beta mRNA increase was not prevented by protein synthesis inhibitors but was prevented by the addition of cyclic AMP analogs. In the presence of RA, cyclic AMP analogs also greatly reduced the RAR alpha and RAR gamma mRNA levels, even though cyclic AMP analogs alone did not alter these mRNA levels. The addition of either RA or RA plus cyclic AMP analogs did not result in changes in the three RAR mRNA half-lives. These results suggest that agents which elevate the internal cyclic AMP concentration may also affect the cellular response to RA by altering the expression of the RARs.
在向F9畸胎瘤干细胞添加视黄酸(RA)后,视黄酸受体α(RARα)和RARγ的稳态mRNA水平随时间保持相对恒定。相比之下,稳态RARβ mRNA水平在添加RA后12小时内开始升高,并在48小时时达到高20倍的水平。这种与RA相关的RARβ mRNA增加不受蛋白质合成抑制剂的影响,但可通过添加环磷酸腺苷类似物来阻止。在存在RA的情况下,环磷酸腺苷类似物也大大降低了RARα和RARγ mRNA水平,尽管单独的环磷酸腺苷类似物不会改变这些mRNA水平。添加RA或RA加环磷酸腺苷类似物均未导致三种RAR mRNA半衰期的变化。这些结果表明,提高细胞内环磷酸腺苷浓度的试剂也可能通过改变RAR的表达来影响细胞对RA的反应。