Gao Min, Wang Rui, Yu Fabiao, You Jinmao, Chen Lingxin
Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Research Centre for Coastal Environmental Engineering and Technology, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China.
J Mater Chem B. 2018 May 7;6(17):2608-2619. doi: 10.1039/c7tb03200e. Epub 2018 Feb 26.
Ischemia is a pathological condition owing to the deficiency of blood supply to a limited area of tissue. Ischemia can induce burst production of reactive oxygen species and lead to oxidative damage. As a family member of reactive sulfur species, sulfane sulfur plays important physiological roles in many biological events including synthesis of cofactors, modulation of enzyme activities, sulfuration of tRNA, and especially regulation of the intracellular redox state. We hypothesize that the endogenous level of sulfane sulfur will be adjusted to deal with ischemia-induced oxidative damage. Therefore, the bioimaging of sulfane sulfur real-time changes during ischemia is important for better understanding its physiological processes. Herein, we describe the development of a mitochondria-targeted fluorescent probe Mito-SH that allowed for selective and sensitive detection of sulfane sulfur. Mito-SH is designed on the basis of the tautomerization of sulfane sulfur to thiosulfoxide, which ensures its high selectivity and sensitivity. A lipophilic triphenylphosphonium cation is selected as the mitochondria-targeted moiety, which can precisely navigate Mito-SH into mitochondria. The emission profile of azo-BODIPY fluorophore locates at the near-infrared region, which deeply penetrates tissue and effectively avoids the interference of biological background. Mito-SH exhibits the desirable combination of selectivity, sensitivity and excellent fluorescence response upon reaction with sulfane sulfur in cells. By employing Mito-SH, we evaluate the real-time sulfane sulfur dynamic changes under oxygen-glucose deprivation. Finally, Mito-SH has been successfully used for imaging sulfane sulfur changes caused by acute ischemia in mice.
缺血是一种由于有限组织区域血液供应不足而导致的病理状态。缺血可诱导活性氧的爆发性产生并导致氧化损伤。作为活性硫物种家族的一员，次磺酸硫在许多生物学事件中发挥重要生理作用，包括辅因子的合成、酶活性的调节、tRNA的硫化，尤其是细胞内氧化还原状态的调节。我们假设内源性次磺酸硫水平会被调节以应对缺血诱导的氧化损伤。因此，缺血期间次磺酸硫实时变化的生物成像对于更好地理解其生理过程很重要。在此，我们描述了一种线粒体靶向荧光探针Mito-SH的开发，该探针能够选择性和灵敏地检测次磺酸硫。Mito-SH是基于次磺酸硫向硫代亚砜的互变异构设计的，这确保了其高选择性和灵敏度。选择亲脂性三苯基膦阳离子作为线粒体靶向部分，它可以精确地将Mito-SH导向线粒体。偶氮-硼二吡咯荧光团的发射光谱位于近红外区域，能深入穿透组织并有效避免生物背景的干扰。Mito-SH在与细胞中的次磺酸硫反应时表现出理想的选择性、灵敏度和出色的荧光响应。通过使用Mito-SH，我们评估了氧糖剥夺下次磺酸硫的实时动态变化。最后，Mito-SH已成功用于成像小鼠急性缺血引起的次磺酸硫变化。
