Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 0B8.
Chem Rev. 2020 Dec 9;120(23):12757-12787. doi: 10.1021/acs.chemrev.0c00761. Epub 2020 Nov 19.
Our understanding of lipid peroxidation in biology and medicine is rapidly evolving, as it is increasingly implicated in various diseases but also recognized as a key part of normal cell function, signaling, and death (ferroptosis). Not surprisingly, the root and consequences of lipid peroxidation have garnered increasing attention from multiple disciplines in recent years. Here we "connect the dots" between the fundamental chemistry underpinning the cascade reactions of lipid peroxidation (enzymatic or free radical), the reactive nature of the products formed (lipid-derived electrophiles), and the biological targets and mechanisms associated with these products that culminate in cellular responses. We additionally bring light to the use of highly sensitive, fluorescence-based methodologies. Stemming from the foundational concepts in chemistry and biology, these methodologies enable visualizing and quantifying each reaction in the cascade in a cellular and ultimately tissue context, toward deciphering the connections between the chemistry and physiology of lipid peroxidation. The review offers a platform in which the chemistry and biomedical research communities can access a comprehensive summary of fundamental concepts regarding lipid peroxidation, experimental tools for the study of such processes, as well as the recent discoveries by leading investigators with an emphasis on significant open questions.
我们对生物学和医学中脂质过氧化的理解正在迅速发展，因为它越来越多地与各种疾病有关联，但也被认为是正常细胞功能、信号传递和死亡（铁死亡）的关键部分。毫不奇怪，近年来，脂质过氧化的根源和后果引起了多个学科的越来越多的关注。在这里，我们在脂质过氧化级联反应（酶促或自由基）的基础化学、形成的产物的反应性（脂质衍生的亲电试剂）以及与这些产物相关的生物靶标和机制之间“连接点”，这些产物最终导致细胞反应。我们还介绍了高灵敏度、基于荧光的方法的应用。这些方法源自化学和生物学的基础概念，使我们能够在细胞和最终组织环境中可视化和量化级联中的每个反应，以揭示脂质过氧化的化学和生理学之间的联系。该综述为化学和生物医学研究界提供了一个平台，使他们能够全面了解脂质过氧化的基本概念、研究此类过程的实验工具，以及主要研究人员的最新发现，重点是突出存在的一些开放性问题。
