Adipose differentiation-related protein is not involved in hypoxia inducible factor-1-induced lipid accumulation under hypoxia.
Adipose differentiation-related protein is not involved in hypoxia inducible factor-1-induced lipid accumulation under hypoxia.
复制标题
脂肪分化相关蛋白不参与缺氧诱导因子1诱导的缺氧脂质积累。
DOI：
10.3892/mmr.2015.4488
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发表时间：
2015-12
影响因子：
3.4
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Shen G;Ning N;Zhao X;Liu X;Wang G;Wang T;Zhao R;Yang C;Wang D;Gong P;Shen Y;Sun Y;Zhao X;Jin Y;Yang W;He Y;Zhang L;Jin X;Li X
越来越多的证据表明，低氧诱导因子-1(HIF1)在低氧诱导的脂质堆积中起重要作用，这是实体肿瘤的共同特征，但其作用仍未完全阐明。脂肪分化相关蛋白(AdRP)是一种脂滴结构蛋白，在低氧条件下表达上调。本研究以MCF7乳腺癌细胞为研究对象，研究了ADRP在低氧诱导的脂质堆积中的作用。结果表明，低氧以HIF1依赖的方式诱导ADRP基因表达。ADRP的mRNA和蛋白水平的增加伴随着HIF1a活性的增加。此外，在靶向HIF1a的siRNA存在下，ADRP的mRNA和蛋白水平显著降低。通过双荧光素酶报告实验和染色质免疫沉淀实验，本研究证实了adrp是HIF1的直接靶基因，并鉴定了位于adrp基因转录起始点上游33bp的功能性缺氧反应元件。此外，本研究还证实了adrp在低密度脂蛋白(LDL)和低密度脂蛋白(Very-LDL)摄取诱导的低氧下脂质堆积中的作用。在低氧条件下，抑制ADRP并不能减少HIF1诱导的脂质堆积。综上所述，这些结果表明ADRP可能不参与HIF1诱导的脂质堆积。
Increasing evidence has showed that hypoxia inducible factor-1 (HIF1) has an important role in hypoxia-induced lipid accumulation, a common feature of solid tumors; however, its role remains to be fully elucidated. Adipose differentiation-related protein (ADRP), a structural protein of lipid droplets, is found to be upregulated under hypoxic conditions. In the present study, an MCF7 breast cancer cell line was used to study the role of ADRP in hypoxia-induced lipid accumulation. It was demonstrated that hypoxia induced the gene expression of ADRP in a HIF1-dependent manner. Increases in the mRNA and protein levels of ADRP was accompanied by increased HIF1A activity. In addition, a significant decrease in the mRNA and protein levels of ADRP were detected in presence of siRNA targeting HIF1A. Using a dual-luciferase reporting experiment and chromatin immunoprecipitation assay, the present study demonstrated that ADRP is a direct target gene of HIF1, and identified a functional hypoxia response element localized 33 bp upstream of the transcriptional start site of the ADRP gene. Furthermore, the present study demonstrated the role of ADRP in low density liporotein (LDL) and very-LDL uptake-induced lipid accumulation under hypoxia. The knockdown of ADRP did not reduce HIF1-induced lipid accumulation under hypoxia. Together, these results showed that ADRP may be not involved in HIF1-induced lipid accumulation.