Zheng Z, Messi M L, Delbono O
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Mech Ageing Dev. 2001 Apr 15;122(4):373-84. doi: 10.1016/s0047-6374(00)00236-0.
In the present work, we investigated whether IGF-1 regulates the transcription of the genes encoding the L-type Ca2+ channel (DHPR) channel and RyR1 in young adult and senescent mice. To this end, a transgenic mouse model overexpressing IGF-1 exclusively in skeletal muscle (S1S2) was studied at different ages and the results were compared with wild type age-matched mice (FVB). We found that ribosomal RNA expression did not change significantly either with age or IGF-1 according to ribonuclease protection and nuclear run-on transcription assays. Transgenic overexpression of IGF-1 resulted in marked increases in skeletal muscle DHPR alpha(1S) and RyR1 mRNA in young and old mice and in enhanced DHPR alpha(1S) nuclear transcription in skeletal muscles from young mice when normalized to 28S ribosomal RNA. These results support the concept that IGF-1 regulates the expression of DHPR by modulating DHPR alpha(1S) nuclear transcription.
在本研究中，我们探究了胰岛素样生长因子-1（IGF-1）是否调控年轻成年小鼠和衰老小鼠中编码L型钙通道（二氢吡啶受体，DHPR）和兰尼碱受体1（RyR1）的基因转录。为此，我们研究了一种仅在骨骼肌中过表达IGF-1的转基因小鼠模型（S1S2）在不同年龄时的情况，并将结果与年龄匹配的野生型小鼠（FVB）进行比较。根据核糖核酸酶保护和细胞核连续转录分析，我们发现核糖体RNA表达无论随年龄还是IGF-1都没有显著变化。IGF-1的转基因过表达导致年轻和老年小鼠骨骼肌中DHPR α(1S)和RyR1 mRNA显著增加，并且在以28S核糖体RNA标准化后，年轻小鼠骨骼肌中DHPR α(1S)的细胞核转录增强。这些结果支持了IGF-1通过调节DHPR α(1S)细胞核转录来调控DHPR表达的观点。
