Palmitate Induces TRB3 Expression and Promotes Apoptosis in Human Liver Cells
Palmitate Induces TRB3 Expression and Promotes Apoptosis in Human Liver Cells
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DOI：
10.1159/000358655
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发表时间：
2014-03
影响因子：
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通讯作者：
Weihui Yan;Ying Wang;Yongtao Xiao;Jie Wen;Jiang Wu;Lei Du;W. Cai
中科院分区：
文献类型：
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作者：
Weihui Yan;Ying Wang;Yongtao Xiao;Jie Wen;Jiang Wu;Lei Du;W. Cai
背景/目的：肠外营养相关性肝病（PNALD）是需要长期肠外营养的患者的主要并发症。PNALD的治疗选择有限，其发病机制尚不清楚。Tribbles同源物3 （TRB3）是一种调节许多信号转导级联的假激酶，可能参与PNALD的发病机制。本研究的目的是研究TRB3在棕榈酸盐诱导的人肝细胞系L02内质网应激中的作用。方法：用棕榈酸酯处理L02细胞，观察其对细胞活力、线粒体膜电位、凋亡及TRB3表达的影响。通过在L02细胞中短暂过表达TRB3，以及TRB3与Akt信号的相互作用，我们也研究了TRB3的作用。结果：棕榈酸盐诱导L02细胞内质网应激和凋亡。棕榈酸相关内质网应激在mRNA和蛋白水平上显著诱导TRB3表达。TRB3的过表达增强了棕榈酸盐的有害作用，这与磷酸化akt水平的降低有关。结论：TRB3是棕榈酸盐诱导人肝细胞凋亡的重要介质，提示其可能参与PNALD的分子机制。
Background/Aims: Parenteral nutrition-associated liver disease (PNALD) is a major complication for patients who require long-term parenteral nutrition. Treatment options for PNALD are limited and its pathogenesis is poorly understood. Tribbles homolog 3 (TRB3) is a pseudokinase that modulates many signal transduction cascades and may be involved in the pathogenesis of PNALD. The aim of this study was to examine the role of TRB3 in palmitate-induced endoplasmic reticulum (ER) stress, in the human liver cell line L02. Methods: L02 cells were treated with palmitate, and its effect on cell viability, mitochondrial membrane potential, apoptosis and TRB3 expression were assessed. The role of TRB3 was also studied using transient overexpression of TRB3 in L02 cells, as well as its interaction with Akt signaling. Results: We found that palmitate induced ER stress and apoptosis in L02 cells. Palmitate-associated ER stress was accompanied by a significant induction of TRB3 expression at the mRNA and protein level. Overexpression of TRB3 potentiated the deleterious effects of palmitate, which was associated with decreased levels of phospho-Akt. Conclusions: TRB3 is an important mediator of palmitate-induced apoptosis in human liver cells, suggesting that it may also be involved in the molecular mechanism underlying PNALD.