Department of Chemistry and Quebec Center for Advanced Materials (QCAM/CQMF), McGill University, 801 Sherbrooke Street West, Montreal, QC, Canada H3A 0B8.
Department of Chemistry and Quebec Center for Advanced Materials (QCAM/CQMF), McGill University, 801 Sherbrooke Street West, Montreal, QC, Canada H3A 0B8.
Free Radic Biol Med. 2018 Nov 20;128:124-136. doi: 10.1016/j.freeradbiomed.2018.04.006. Epub 2018 Apr 9.
Lipid peroxidation of polyunsaturated fatty acids in cells may occur via their catalytic autoxidation through peroxyl radicals under oxidative stress conditions. Lipid peroxidation is related to a number of pathologies, and may be invoked in new forms of regulated cell death, yet it may also have beneficial roles in cell signaling cascades. Antioxidants are a natural line of defense against lipid peroxidation, and may accordingly impact the biological outcome associated with the redox chemistry of lipid peroxidation. Critical to unraveling the physiological and pathological role of lipid peroxidation is the development of novel probes with the partition, chemical sensitivity and more importantly, molecular specificity, enabling the spatial and temporal imaging of peroxyl radicals in the lipid membranes of live cells, reporting on the redox status of the cell membrane. This review describes our recent progress to visualize lipid peroxidation in model membrane systems and in live cell studies. Our work portrays the mechanistic insight leading to the development of a highly sensitive probe to monitor lipid peroxyl radicals (LOO). It also describes technical aspects including reagents and fluorescence microscopy methodologies to consider in order to achieve the much sought after monitoring of rates of lipid peroxyl radical production in live cell studies, be it under oxidative stress but also under cell homeostasis. This review seeks to bring attention to the study of lipid redox reactions and to lay the groundwork for the adoption of fluorogenic antioxidant probeshancement and maximum intensity recorded in turn provide a benchmark to estimate, when compared to the control BODIPY dye lacking the intramolecular PeT based switch, the overall exte and related fluorescence microscopy methods toward gaining rich spatiotemporal information on lipid peroxidation in live cells.
细胞中多不饱和脂肪酸的脂质过氧化可能通过氧化应激条件下过氧自由基的催化自动氧化发生。脂质过氧化与许多病理有关，可能在新形式的调节性细胞死亡中被调用，但它也可能在细胞信号级联中发挥有益作用。抗氧化剂是防止脂质过氧化的天然防线，因此可能会影响与脂质过氧化的氧化还原化学相关的生物学结果。揭示脂质过氧化的生理和病理作用的关键是开发具有分配、化学敏感性的新型探针，更重要的是，具有分子特异性，使活细胞中脂质膜中的过氧自由基能够进行时空成像，报告细胞膜的氧化还原状态。本综述描述了我们最近在模型膜系统和活细胞研究中可视化脂质过氧化的进展。我们的工作描绘了导致开发高度敏感探针以监测脂质过氧自由基（LOO）的机制见解。它还描述了技术方面，包括试剂和荧光显微镜方法学，以在活细胞研究中实现对脂质过氧自由基产生率的梦寐以求的监测，无论是在氧化应激下还是在细胞稳态下。本综述旨在引起人们对脂质氧化还原反应的研究的关注，并为采用荧光抗氧化探针的增强和最大强度记录奠定基础，以便与缺乏基于 PeT 的分子内开关的对照 BODIPY 染料进行比较，提供一个基准来估计与控制 BODIPY 染料相比，总体扩展和相关的荧光显微镜方法为活细胞中的脂质过氧化提供丰富的时空信息。
