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代谢组学驱动的腺病毒诱导细胞死亡的调控。

Metabolome-Driven Regulation of Adenovirus-Induced Cell Death.

机构信息

Group of Experimental Biotherapy and Diagnostic, Institute for Regenerative Medicine, World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University, 119991 Moscow, Russia.

Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

出版信息

Int J Mol Sci. 2021 Jan 5;22(1):464. doi: 10.3390/ijms22010464.

Abstract

A viral infection that involves virus invasion, protein synthesis, and virion assembly is typically accompanied by sharp fluctuations in the intracellular levels of metabolites. Under certain conditions, dramatic metabolic shifts can result in various types of cell death. Here, we review different types of adenovirus-induced cell death associated with changes in metabolic profiles of the infected cells. As evidenced by experimental data, in most cases changes in the metabolome precede cell death rather than represent its consequence. In our previous study, the induction of autophagic cell death was observed following adenovirus-mediated lactate production, acetyl-CoA accumulation, and ATP release, while apoptosis was demonstrated to be modulated by alterations in acetate and asparagine metabolism. On the other hand, adenovirus-induced ROS production and ATP depletion were demonstrated to play a significant role in the process of necrotic cell death. Interestingly, the accumulation of ceramide compounds was found to contribute to the induction of all the three types of cell death mentioned above. Eventually, the characterization of metabolite analysis could help in uncovering the molecular mechanism of adenovirus-mediated cell death induction and contribute to the development of efficacious oncolytic adenoviral vectors.

摘要

病毒感染通常伴随着细胞内代谢物水平的剧烈波动,包括病毒入侵、蛋白质合成和病毒粒子组装。在某些条件下,剧烈的代谢转变可能导致各种类型的细胞死亡。在这里,我们回顾了与感染细胞代谢谱变化相关的不同类型的腺病毒诱导的细胞死亡。实验数据表明,在大多数情况下,代谢组的变化先于细胞死亡发生,而不是其结果。在我们之前的研究中,观察到腺病毒介导的乳酸产生、乙酰辅酶 A 积累和 ATP 释放后会诱导自噬性细胞死亡,而凋亡被证明受到乙酸盐和天冬酰胺代谢改变的调节。另一方面,腺病毒诱导的 ROS 产生和 ATP 耗竭被证明在坏死性细胞死亡过程中发挥重要作用。有趣的是,神经酰胺化合物的积累被发现有助于诱导上述三种类型的细胞死亡。最终,代谢物分析的特征可以帮助揭示腺病毒介导的细胞死亡诱导的分子机制,并有助于开发有效的溶瘤腺病毒载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f76/7796492/08fade89f16e/ijms-22-00464-g001.jpg

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