Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology.
Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology.
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化学发生学方法探测氧化还原途径：心血管药理学和毒理学的意义。
DOI：
10.1146/annurev-pharmtox-012221-082339
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发表时间：
2022-01-06
影响因子：
12.5
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中科院分区：
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化学遗传学是指通过提供或抑制重组蛋白的特定生化刺激来动态调节重组蛋白活性的实验系统。化学遗传学工具允许对特定的信号分子进行精确的动态控制，以描绘这些分子在生理和疾病中的作用。酵母d-氨基酸氧化酶(DAAO)仅在d-氨基酸存在的情况下才能产生过氧化氢，从而实现对细胞内氧化还原平衡的化学调控。生物传感器的进步使这些信号分子的精确定量成为可能。化学遗传学方法与生物传感器方法的结合开辟了新的研究路线，使分析细胞内调节生理和病理细胞反应的氧化还原途径成为可能。我们预计，新开发的转基因化学发生模型将允许在不同的细胞和组织中动态调节细胞氧化还原平衡，并将有助于识别和验证涉及生理性氧化还原途径和病理性氧化应激的新的治疗靶点。
Chemogenetics refers to experimental systems that dynamically regulate the activity of a recombinant protein by providing or withholding the protein’s specific biochemical stimulus. Chemogenetic tools permit precise dynamic control of specific signaling molecules to delineate the roles of those molecules in physiology and disease. Yeast d-amino acid oxidase (DAAO) enables chemogenetic manipulation of intracellular redox balance by generating hydrogen peroxide only in the presence of d-amino acids. Advances in biosensors have allowed the precise quantitation of these signaling molecules. The combination of chemogenetic approaches with biosensor methodologies has opened up new lines of investigation, allowing the analysis of intracellular redox pathways that modulate physiological and pathological cell responses. We anticipate that newly developed transgenic chemogenetic models will permit dynamic modulation of cellular redox balance in diverse cells and tissues and will facilitate the identification and validation of novel therapeutic targets involved in both physiological redox pathways and pathological oxidative stress.