Association of SND1 protein to low density lipid droplets in liver steatosis
Association of SND1 protein to low density lipid droplets in liver steatosis
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DOI：
10.1007/s13105-010-0011-0
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发表时间：
2010-03-01
影响因子：
3.4
通讯作者：
Fresnedo, O.
中科院分区：
文献类型：
--
作者：
Garcia-Arcos, I.;Rueda, Y.;Fresnedo, O.
尽管SND p102的人类同源物p100共激活蛋白最初被描述为核蛋白，但p100共激活蛋白家族成员在哺乳动物细胞中具有非核定位，具有活性脂质处理、储存和分泌。然而，它们在脂质稳态中的作用仍然没有得到解决。在这里，我们调查的大鼠同源SND p102（也称为SND1）的分布及其与新形成的脂滴在肝实质和培养的肝细胞。蔗糖梯度分离显示SND p102与内质网和高尔基体标记共分离。这种共分馏在再生脂肪变性大鼠肝脏中没有改变。然而，SND p102也检测到再生肝的脂滴，显示出特定的方向性最低密度的。培养肝细胞的共聚焦显微镜证实了梯度分离的结果。此外，p100辅激活剂始终遇到微粒体和脂滴在控制和油酸酯处理的HepG2细胞。在两种条件下，肝细胞中SND p102的总量相似，表明蛋白质的特异性易位。我们的研究结果表明，SND p102和人p100辅激活因子在肝细胞中具有普遍的细胞质分布，并且脂肪生成条件促进SND p102从其他细胞隔室靶向特定的低密度脂滴。
Although the human homologue of SND p102, p100 coactivator, was initially described as a nuclear protein, the p100 coactivator protein family members have non-nuclear localization in mammalian cells with active lipid handling, storage, and secretion. However, their role in lipid homeostasis remains unresolved. Here, we investigate the distribution of the rat homologue SND p102 (also called SND1) and its association with newly formed lipid droplets in the liver parenchyma and cultured hepatocytes. Sucrose gradient fractionation showed that SND p102 cofractionated with endoplasmic reticulum and Golgi markers. Such cofractionation was not altered in regenerating steatotic rat liver. However, SND p102 was also detected in lipid droplets from regenerating liver, showing a specific directionalization to the least dense ones. Confocal microscopy of cultured hepatocytes confirmed the findings of gradient fractionation. In addition, p100 coactivator was consistently encountered in microsomes and lipid droplets in control and oleate-treated HepG2 cells. The total amount of SND p102 in hepatocytes was similar in both conditions, suggesting a specific translocation of the protein. Our findings indicate that SND p102 and the human p100 coactivator have a ubiquitous cytoplasmic distribution in hepatocytes and that steatogenic conditions promote the targeting of SND p102 from other cell compartments to specific low density lipid droplets.