| 邱秀英韩继武△ 李姣姣.PI3K/Akt 及其靶蛋白FOXO1 与非酒精性脂肪性肝病[J].,2012,12(23):4584-4587 |
| PI3K/Akt 及其靶蛋白FOXO1 与非酒精性脂肪性肝病 |
| The Relationship between PI3K/Akt and its Target Protein FOXO1 and theNonalcohic Fatty Liver Disease |
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| DOI： |
| 中文关键词: 非酒精性脂肪肝 PI3K Akt Foxo1 |
| 英文关键词: Nonalcoholic fatty liver PI3K Akt Foxo1 |
| 基金项目: |
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| 中文摘要: |
| FOXO 转录因子是Forkhead 蛋白大家族的一个亚群，在人类的4 个同源基因中包括FoxO1、FoxO2、FoxO3a 和FoxO4。
FoxO 蛋白质通过丝氨酸或苏氨酸以及赖氨酸残基的磷酸化和乙酰化等后转录修饰后而发挥作用。其中Foxo1 是含有高度保守
DNA 结合位点的核转录蛋白，其主要功能是磷脂酰肌醇3- 激酶（PI3K）/ 蛋白激酶B(Akt)的底物，在胰岛素信号转导中起负性调
节作用，Foxo1 通过介导胰岛素依赖性微粒体甘油三酯转运蛋白（MTP）的表达，影响肝脏装配和分泌极低密度脂蛋白（VLDL）,维
持脂代谢稳定。在胰岛素抵抗和脂肪肝状态下，肝细胞核内Foxo1 表达明显升高，引起高甘油三酯血症和脂肪肝。有针对性的干
预PI3K/Akt 及Foxo1 的表达，可能从分子机制上为非酒精性脂肪肝的防治提供广阔前景。 |
| 英文摘要: |
| FOXO transcription factors are a subgroup of the Forkhead protein family, and it contains four homologous genes,
namely FOXO1, FOXO2, FOXO3 and FOXO4 in the human genome. FOXO protein were activated by post translational modification
such as the phosphorylation of serine or threonine and acetylation of lysine residues. Among them FOXO1 is the nuclear transcription
protein which contains highly conserved DNA binding sequence. It acts as a substrate of phosphatidylinositol 3-kinases (PI3K) / protein
kinase B (Akt),and plays a negative regulatory role in insulin Signal transduction pathway. Foxo1 maintains the lipid metabolism stable
through mediating the expression of insulin-dependent microsomal and then influencing the assembling and secretion of VLDL. In the
condition of insulin resistance and fatty liver, the expression of liver cell nuclear Foxo1 increased significantly, therefore resulted in high
triglycerides and fatty liver. Targeting interference on PI3K/Akt and Foxo1 expression may provide a broad prospect for the treatment of
nonalcoholic fatty liver disease in the aspect of molecular mechanism. |
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