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    HIV-1 Tat蛋白激活AKT信号调节肝细胞脂肪代谢

    HIV-1 Tat enhances lipid metabolism in human hepatocytes via activating AKT signaling

    • 摘要: 目的 研究人类免疫缺陷病毒1型(HIV-1)Tat蛋白在调节人肝细胞脂肪代谢基因表达中的作用。方法 根据人肝脏中调节脂质生成的转录因子固醇调节元件结合蛋白-1c(Serbp1c)和碳水化合物调节元件结合蛋白(ChREBP)及其下游基因(Dgat、Lpk、Fasn和Scd-1)的cDNA碱基序列,设计并合成引物;培养人肝细胞株LO2,PI3K/AKT信号通路抑制剂PD98059预处理,Tat蛋白刺激细胞后,提取不同时间点的细胞总RNA,逆转录生成cDNA,应用定量PCR(q-PCR)检测人肝细胞中Srebp1c和ChREBP及其下游基因Dgat、Lpk、Fasn和Scd-1mRNA转录水平。结果 Tat蛋白显著增强人肝细胞中Srebp1c和ChREBP及其下游基因Dgat、Lpk、Fasn和Scd-1 mRNA表达水平,在刺激6h后达到峰值;而且PI3K/AKT信号通路抑制剂PD98059显著下调Tat诱导的Srebp1c和ChREBP及其下游基因Dgat、Lpk、Fasn和Scd-1基因转录。结论 HIV Tat蛋白在人肝细胞中对脂质生成有促进作用,进而调节肝细胞脂肪代谢。

       

      Abstract: Objective To explore the role of human immunodeficiency virus type 1 (HIV-1) Tat protein in lipid metabolism in human hepatocytes. Methods Primers were designed and synthesized based on the cDNA base sequence of the transcription factor sterol regulatory element binding protein-1c (Serbp1c) and carbohydrate-responsive element binding protein (ChREBP) as well as their target genes (Dgat, Lpk, Fasnand Scd-1), which regulate the regeneration of lipids in human liver. The human hepatocyte cell line LO2 was stimulated with Tat proteins at different time points. Total RNA was extracted and cDNA was generated by reverse transcription. Quantitative PCR (q-PCR) was used to detect the transcription levels of Srebp1c and ChREBP and their downstream genes Dgat, Lpk, Fasn and Scd-1 mRNA in human hepatocytes. Results With the stimulation of HIV-1 Tat protein, the expression levels of Srebp1c and ChREBP and their downstream genes Dgat, Lpk, Fasn and Scd-1 mRNA in human hepatocytes increased significantly, and reached the peak after 6 h. Conclusion HIV-1 Tat protein promotes the regeneration of lipids in human hepatocytes, and regulates the lipid metabolism of hepatocytes.

       

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