Natural Medicine Research & Development Center, Lanzhou Jiaotong University, Lanzhou 730070, China.
School of Chemistry and Chemical Engineering, Nanjing University of Science & Technology, Nanjing 210094, China.
Biosensors (Basel). 2023 Aug 13;13(8):811. doi: 10.3390/bios13080811.
The modulation of numerous signaling pathways is orchestrated by redox regulation of cellular environments. Maintaining dynamic redox homeostasis is of utmost importance for human health, given the common occurrence of altered redox status in various pathological conditions. The cardinal component of the thioredoxin system, mammalian thioredoxin reductase (TrxR) plays a vital role in supporting various physiological functions; however, its malfunction, disrupting redox balance, is intimately associated with the pathogenesis of multiple diseases. Accordingly, the dynamic monitoring of TrxR of live organisms represents a powerful direction to facilitate the comprehensive understanding and exploration of the profound significance of redox biology in cellular processes. A number of classic assays have been developed for the determination of TrxR activity in biological samples, yet their application is constrained when exploring the real-time dynamics of TrxR activity in live organisms. Fluorescent probes offer several advantages for in situ imaging and the quantification of biological targets, such as non-destructiveness, real-time analysis, and high spatiotemporal resolution. These benefits facilitate the transition from a poise to a flux understanding of cellular targets, further advancing scientific studies in related fields. This review aims to introduce the progress in the development and application of TrxR fluorescent probes in the past years, and it mainly focuses on analyzing their reaction mechanisms, construction strategies, and potential drawbacks. Finally, this study discusses the critical challenges and issues encountered during the development of selective TrxR probes and proposes future directions for their advancement. We anticipate the comprehensive analysis of the present TrxR probes will offer some glitters of enlightenment, and we also expect that this review may shed light on the design and development of novel TrxR probes.
众多信号通路的调节是由细胞环境的氧化还原调节来协调的。考虑到在各种病理条件下氧化还原状态的改变很常见，维持动态氧化还原平衡对人类健康至关重要。硫氧还蛋白系统的主要组成部分哺乳动物硫氧还蛋白还原酶（TrxR）在支持各种生理功能方面起着至关重要的作用；然而，其功能障碍破坏了氧化还原平衡，与多种疾病的发病机制密切相关。因此，动态监测活生物体中的 TrxR 代表了一种强大的方向，可以促进对氧化还原生物学在细胞过程中的深远意义的全面理解和探索。已经开发了许多经典测定来测定生物样品中的 TrxR 活性，但是当探索活生物体中 TrxR 活性的实时动态时，它们的应用受到限制。荧光探针为原位成像和生物靶标的定量提供了许多优势，例如非破坏性、实时分析和高时空分辨率。这些优点有助于从平衡态向通量态理解细胞靶标转变，进一步推动相关领域的科学研究。本综述旨在介绍过去几年中 TrxR 荧光探针的开发和应用进展，主要分析它们的反应机制、构建策略和潜在的缺点。最后，本研究讨论了选择性 TrxR 探针开发过程中遇到的关键挑战和问题，并提出了未来的发展方向。我们期望对当前 TrxR 探针的全面分析将提供一些启示，我们也期望本综述可以为新型 TrxR 探针的设计和开发提供一些思路。
