Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic reticulum stress and autophagy
Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic reticulum stress and autophagy
复制标题
棕榈酸通过内质网应激和自噬诱导人成骨样 Saos-2 细胞凋亡
DOI：
10.1007/s12192-018-0936-8
复制
发表时间：
2018-11-01
影响因子：
3.8
通讯作者：
Gu, Xiang
中科院分区：
文献类型：
--
作者：
Yang, Lei;Guan, Gaopeng;Gu, Xiang
棕榈酸（PA）是食物中最常见的饱和长链脂肪酸，可引起细胞凋亡。然而，PA毒性的分子机制知之甚少。在本研究中，我们探讨PA对人成骨样Saos-2细胞增殖和凋亡的影响，并揭示参与这一过程的信号通路。我们的研究表明，内质网（ER）应激和自噬参与PA诱导的Saos-2细胞凋亡。我们发现，PA抑制Saos-2细胞的活力在剂量和时间依赖性的方式。同时，PA诱导ER应激标记基因（葡萄糖调节蛋白78（GRP 78）和CCAAT/增强子结合蛋白同源蛋白（CHOP））的表达，改变自噬相关基因（微管相关蛋白1轻链3（LC 3），ATG 5，p62和Beclin）的表达，促进凋亡相关基因（Caspase 3和BAX）的表达，并影响自噬通量。用4-PBA抑制ER应激可减少PA诱导的细胞凋亡，激活自噬，并增加Caspase 3和BAX的表达。用3-MA抑制自噬可减弱PA和ER应激诱导的细胞凋亡和凋亡相关基因（Caspase 3和BAX）的表达，但对ER应激无明显影响，但CHOP表达下调。综上所述，我们的研究结果表明，PA诱导的Saos-2细胞凋亡是通过ER应激和自噬激活的，并且自噬的激活在此过程中依赖于ER应激。
Palmitic acid (PA) is the most common saturated long-chain fatty acid in food that causes cell apoptosis. However, little is known about the molecular mechanisms of PA toxicity. In this study, we explore the effects of PA on proliferation and apoptosis in human osteoblast-like Saos-2 cells and uncover the signaling pathways involved in the process. Our study showed that endoplasmic reticulum (ER) stress and autophagy are involved in PA-induced Saos-2 cell apoptosis. We found that PA inhibited the viability of Saos-2 cells in a dose- and time-dependent manner. At the same time, PA induced the expression of ER stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)), altered autophagy-related gene expression (microtubule-associated protein 1 light chain 3 (LC3), ATG5, p62, and Beclin), promoted apoptosis-related gene expression (Caspase 3 and BAX), and affected autophagic flux. Inhibiting ER stress with 4-PBA diminished the PA-induced cell apoptosis, activated autophagy, and increased the expression of Caspase 3 and BAX. Inhibiting autophagy with 3-MA attenuated the PA and ER stress-induced cell apoptosis and the apoptosis-related gene expression (Caspase 3 and BAX), but seemed to have no obvious effects on ER stress, although the CHOP expression was downregulated. Taken together, our results suggest that PA-induced Saos-2 cell apoptosis is activated via ER stress and autophagy, and the activation of autophagy depends on the ER stress during this process.