Acrylamide inhibits autophagy, induces apoptosis and alters cellular metabolic profiles
Acrylamide inhibits autophagy, induces apoptosis and alters cellular metabolic profiles
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丙烯酰胺抑制自噬、诱导细胞凋亡并改变细胞代谢特征。
DOI：
10.1016/j.ecoenv.2020.111543
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发表时间：
2021-01-15
影响因子：
6.8
通讯作者：
Liu, Rong
中科院分区：
文献类型：
--
作者：
Song, Dan;Xu, Chao;Liu, Rong
丙烯酰胺（Acrylamide， ACR）是富含碳水化合物的食物在高温下热加工过程中产生的，可通过摄入、吸入和皮肤接触直接进入人体。ACR的毒性已被广泛研究。这些研究的主要结果表明，接触ACR可引起动物和人类的神经毒性，并在啮齿动物模型中显示出生殖毒性和致癌性。然而，ACR的毒性机制尚未通过代谢组学方法研究，ACR对自噬的影响尚不清楚。本实验将U2OS细胞用ACR处理6和24 h，收集后进行进一步研究。我们已经证明ACR抑制自噬通量，增加ROS含量。ROS的积累导致细胞凋亡率和炎症因子的分泌增加。此外，根据多种分析模型，在ACR处理的细胞和对照细胞之间的代谢谱存在显著差异。共鉴定出73种关键差异代谢物。它们参与了多种代谢途径。其中，暴露于ACR通过降低糖酵解中间体的水平导致糖酵解/糖异生的衰减，降低了TCA循环的速率，同时提高了几种氨基酸代谢物和脂质代谢物的水平。总之，我们的研究通过代谢组学和多种生物分析方法为ACR引起的细胞毒性提供了有用的证据。
Acrylamide (ACR) is generated during thermal processing of carbohydrate-rich foods at high temperature and can directly enter the body through ingestion, inhalation and skin contact. The toxicity of ACR has been widely studied. The main results of these studies show that exposure to ACR can cause neurotoxicity in both animals and humans, and show reproductive toxicity and carcinogenicity in rodent animal models. However, the mechanism of toxicity of ACR has not been studied by metabolomics approaches, and the effect of ACR on autophagy remains unknown. Here, U2OS cell were treated with ACR 6 and 24 h and collected for further study. We have demonstrated that ACR inhibited autophagic flux, and increased ROS content. Accumulation of ROS resulted in increase of apoptosis rates and secretion of inflammatory factors. In addition, significant differences in metabolic profiles were observed between ACR treated and control cells according to multiple analysis models. A total of 73 key differential metabolites were identified. They were involved in multiple metabolic pathways. Among them, exposure to ACR caused glycolysis/gluconeogenesis attenuation by decreasing levels of glycolytic intermediates, reduced the rate of the TCA cycle, while elevating levels of several amino acid metabolites and lipid metabolites. In summary, our study provides useful evidence of cytotoxicity caused by ACR via metabolomics and multiple bioanalytic methods.