Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, 712100, China. @aliyun.com.
Food Funct. 2017 Dec 13;8(12):4657-4667. doi: 10.1039/c7fo01429e.
Acrylamide (ACR) is a chronic neurotoxin that is generated in high-starch foods during heat processing. Alpha-lipoic acid (LA) is an antioxidant that occurs in most plants and animals. The objective of this study was to reveal the mechanism of ACR-triggered neurotoxicity and identify the protective role of LA in SH-SY5Y cells. In this study, LA restored ACR-stimulated depletion of glutathione content and mitochondrial membrane potential, moderated the activation of inflammatory pathways, and recovered the Keap1/Nrf2 pathway. Moreover, LA upregulated the activities of oxidative phosphorylation complexes and diminished ACR-induced variation in AMPK/GSK3β, Ca disturbance, and ATP depletion. The Sirt1/PGC-1α pathway was inhibited by ACR. Notably, autophagy was activated in the mitochondria-mediated apoptosis induced by ACR, which was also blocked by LA. Overall, our study demonstrated the pivotal roles of the mitochondrial energy metabolism and autophagy in the protective effects of LA and cytotoxicity of ACR in SH-SY5Y cells.
丙烯酰胺（ACR）是一种在高温加工高淀粉食品过程中产生的慢性神经毒素。α-硫辛酸（LA）是一种抗氧化剂，存在于大多数植物和动物中。本研究旨在揭示 ACR 引发的神经毒性的机制，并确定 LA 在 SH-SY5Y 细胞中的保护作用。在这项研究中，LA 恢复了 ACR 刺激引起的谷胱甘肽含量和线粒体膜电位的耗竭，调节了炎症途径的激活，并恢复了 Keap1/Nrf2 途径。此外，LA 上调了氧化磷酸化复合物的活性，并减少了 ACR 诱导的 AMPK/GSK3β、Ca 紊乱和 ATP 耗竭的变化。ACR 抑制了 Sirt1/PGC-1α 途径。值得注意的是，ACR 诱导的线粒体介导的细胞凋亡中激活了自噬，LA 也阻断了自噬。总的来说，我们的研究表明线粒体能量代谢和自噬在 LA 的保护作用和 ACR 在 SH-SY5Y 细胞中的细胞毒性中起着关键作用。
