D-Amino acid oxidase-derived chemogenetic oxidative stress: Unraveling the multi-omic responses to in vivo redox stress

IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Fotios Spyropoulos , Thomas Michel
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引用次数: 0

Abstract

Chemogenetic approaches have been developed to define the mechanisms whereby the intracellular oxidant hydrogen peroxide (H2O2) modulates both physiological and pathological responses. Recombinant yeast D-amino acid oxidase (DAAO) can be exploited to modulate H₂O₂ in target cells and tissues. In vitro studies using cultured cells expressing recombinant DAAO have provided critical new information on the intracellular transport and metabolism of H2O2 with great temporal and spatial resolution. In contrast, in vivo studies using chemogenetic/transgenic animal models have explored the pathological effects of chronically elevated H2O2 in tissues. Coupled with transcriptomic, proteomic, and metabolomic methods, in vivo chemogenetic approaches are providing new insights into the adaptations to oxidative stress. This review of chemogenetic applications focuses on new models of heart failure and neurodegeneration that leverage in vivo chemogenetic modulation of oxidative stress in target tissues to identify new therapeutic targets.

D-氨基酸氧化酶衍生的化学氧化应激:揭示体内氧化还原应激的多组反应
人们已经开发出化学遗传学方法来确定细胞内氧化剂过氧化氢(H2O2)调节生理和病理反应的机制。重组酵母 D-氨基酸氧化酶(DAAO)可用于调节目标细胞和组织中的氢₂O₂。利用表达重组 DAAO 的培养细胞进行的体外研究提供了有关 H2O2 细胞内运输和代谢的重要新信息,并具有很高的时间和空间分辨率。相反,利用化学遗传/转基因动物模型进行的体内研究则探讨了组织中长期升高的 H2O2 的病理效应。结合转录组学、蛋白质组学和代谢组学方法,体内化学遗传学方法为了解氧化应激的适应性提供了新的视角。本篇关于化学遗传学应用的综述将重点介绍心力衰竭和神经退行性变的新模型,这些模型利用体内化学遗传学调节靶组织中的氧化应激来确定新的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current Opinion in Chemical Biology
Current Opinion in Chemical Biology 生物-生化与分子生物学
CiteScore
13.30
自引率
1.30%
发文量
113
审稿时长
74 days
期刊介绍: COCHBI (Current Opinion in Chemical Biology) is a systematic review journal designed to offer specialists a unique and educational platform. Its goal is to help professionals stay informed about the growing volume of information in the field of Chemical Biology through systematic reviews.
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