Posttranslational processing of SREBP-1 in rat hepatocytes is regulated by insulin and cAMP.
Posttranslational processing of SREBP-1 in rat hepatocytes is regulated by insulin and cAMP.
复制标题
DOI：
10.1016/j.bbrc.2005.04.112
复制
发表时间：
2005-06
影响因子：
3.1
通讯作者：
C. Yellaturu;X. Deng;L. Cagen;H. Wilcox;E. Park;R. Raghow;M. Elam
中科院分区：
文献类型：
--
作者：
C. Yellaturu;X. Deng;L. Cagen;H. Wilcox;E. Park;R. Raghow;M. Elam
胰岛素和cAMP对肝脏和培养的肝细胞中由固醇调节元件结合蛋白（SREBP）介导的从头脂肪酸合成具有相反的作用。为了确定这些试剂是否调节全长SREBP的切割以在原代大鼠肝细胞中产生转录活性N末端片段（nSREBP），构建腺病毒载体（Ad-SREBP-1a）以组成型表达全长SREBP-1a。胰岛素增加nSREBP-1a从其全长前体的生成，而双丁酰（db）-cAMP抑制nSREBP-1a的生成。胰岛素在1h内刺激SREBP-1a的加工，这种作用至少持续24 h。胰岛素对SREBP加工的初始刺激先于Insig-2 mRNA水平的可测量的降低。还用表达核形式SREBP-1c的腺病毒（Ad-nSREBP-1c）感染大鼠肝细胞。胰岛素增加了组成性表达的nSREBP-1c的半衰期，并且胰岛素的这种作用也被db-cAMP抑制。
Insulin and cAMP have opposing effects on de novo fatty acid synthesis in liver and in cultured hepatocytes mediated by sterol-regulatory element binding protein (SREBP). To determine whether these agents regulate the cleavage of full-length SREBP to generate the transcriptionally active N-terminal fragment (nSREBP) in primary rat hepatocytes, an adenoviral vector (Ad-SREBP-1a) was constructed to constitutively express full-length SREBP-1a. Insulin increased, and dibutyryl (db)-cAMP inhibited, generation of nSREBP-1a from its full-length precursor. Insulin stimulated processing of SREBP-1a within 1h, and the effect was sustained for at least 24h. The initial stimulation of SREBP processing by insulin preceded measurable reduction in Insig-2 mRNA levels. Rat hepatocytes were also infected with an adenovirus expressing the nuclear form of SREBP-1c (Ad-nSREBP-1c). Insulin increased the half-life of constitutively expressed nSREBP-1c, and this effect of insulin was also inhibited by db-cAMP.