Sulfane Sulfurs/SO2: Deciphering Redox Environments and Their Implications in Cardio-Protection

项目摘要 心肌细胞中活性硫和活性氧的氧化还原失衡 细胞导致诸如缺血/再灌注（MI/R）损伤和冠状动脉疾病的疾病。再- 已经发现建立氧化还原体内平衡引起强的心脏保护作用如血管舒张， 抗高血压和抗纤维化。然而，这一领域缺乏明确的化学理解， 系统工作。我们的长期目标是破译心脏不同阶段复杂的氧化还原途径， 细胞健康，并利用这些信息通过重建氧化还原稳态来推进心血管治疗。 具体而言，该项目将开发化学工具，以：1）可控地模拟复杂的RSS氧化还原环境 关注硫烷硫; 2）同时检测和利用ROS触发二氧化硫（SO2）相关 细胞洞察力和治疗优势。各种各样的化学工具将被合成， 结构活性关系将使用公布的程序进行优化。然后我们将探索他们的 在MI/R损伤的细胞模型中的心脏保护作用，并测试它们对解读复合物的活力 心血管氧化还原途径。我们希望有前途的候选人将被确定为未来的评估在动物 MI/R和心力衰竭模型。概述的研究将发生在博士明贤的化学生物学 布朗大学的实验室该研究环境包含最先进的工具和设备， 合成化学和生物学。

Project Summary Redox imbalances between reactive sulfur species (RSS) and reactive oxygen species (ROS) in cardiac cells contribute to diseases such as ischemia/reperfusion (MI/R) injury and coronary artery disease. Re- establishing redox homeostasis has been found to cause strong cardioprotective effects such as vasodilation, antihypertension and antifibrosis. However, this field lacks clear chemical understandings as to how these systems work. Our long-term goal is to decipher the complicated redox pathways in various stages of cardiac cell health and use the information to advance cardiovascular therapies by re-establishing redox homeostasis. Specifically, this project will develop chemical tools that: 1) controllably mimic complex RSS redox environments focusing on sulfane sulfurs; and 2) simultaneously detect and utilize ROS to trigger sulfur dioxide (SO2)-related cellular insights and therapeutic advantages. A variety of these chemical tools will be synthesized, and their structure activity relationships will be optimized using published procedures. We will then explore their cardioprotective actions in cell models of MI/R injury and test their viabilities for deciphering complex cardiovascular redox pathways. We expect promising candidates will be identified for future evaluations in animal models of MI/R and heart failure. The outlined research will take place in Dr. Ming Xian’s chemical biology laboratory at Brown University. This research environment contains state-of-the-art tools and equipment for synthetic chemistry and biology.