Biomaterials ( IF 12.8 ) Pub Date : 2018-01-11 , DOI: 10.1016/j.biomaterials.2018.01.011 Min Gao , Rui Wang , Fabiao Yu , Lingxin Chen
As a crucial member in antioxidant regulatory systems, sulfane sulfur plays essential roles in cytoprotective mechanisms by directly eliminating ROS and altering ROS-mediated redox signaling. Despite the rising interests in sulfane sulfur, there only a few bio-compatible methods are available for its direct detection. Moreover, most of the existing methods cannot meet the requirements of real-time detection due to the reactive and labile chemical properties of sulfane sulfur. Therefore, we strive to clarify the mutual relationship between mitochondria sulfane sulfur and ROS under hypoxia stress. Herein, we report a near-infrared fluorescent probe Mito-SeH for the selective imaging of mitochondrial sulfane sulfur in cells and in vivo under hypoxia stress. Mito-SeH includes three moieties: a selenol group (
SeH) as the stronger sulfur-acceptor; a near-infrared azo-BODIPY fluorophore as the fluorescent modulator; a lipophilic alkyltriphenylphosphonium cation as the mitochondrial delivery. Mito-SeH exhibits excellent selectivity and sensitivity towards the detection of mitochondria sulfane sulfur. The hypoxia response behavior of Mito-SeH is evaluated in monolayer cell and three-dimensional multicellular spheroid to clarify the relationship between sulfane sulfur and hypoxia. We confirm that sulfane sulfur protection mechanism against hypoxia is to inhibition of caspase-dependent apoptosis through directly scavenging ROS pathway. The probe is also applied to measurement of sulfane sulfur in ex vivo-dissected organs of hypoxic mouse model, as well as the probe is successfully used for real-time monitoring the changes of sulfane sulfur and ROS in acute ischemia mice model. We suggest that sulfane sulfur may be a novel therapeutic agent for hypoxia-induced injury.中文翻译：
通过靶向线粒体的含硒近红外荧光探针评估亚砜硫的生物效应
作为抗氧化剂调节系统的关键成员，硫磺硫通过直接消除ROS并改变ROS介导的氧化还原信号而在细胞保护机制中发挥重要作用。尽管对硫磺的兴趣日益增加，但仅有几种生物相容性方法可用于直接检测。此外，由于硫磺的反应性和不稳定的化学性质，大多数现有方法不能满足实时检测的要求。因此，我们努力阐明缺氧胁迫下线粒体硫醚硫与活性氧之间的相互关系。在本文中，我们报道了近红外荧光探针Mito-SeH用于在缺氧胁迫下细胞和体内线粒体亚砜硫的选择性成像。Mito-SeH包括三个部分：硒醇基（
SeH）作为更强的硫受体；近红外偶氮-BODIPY荧光团作为荧光调节剂；亲脂性烷基三苯基phosph阳离子作为线粒体传递。Mito-SeH对线粒体亚砜硫的检测显示出极好的选择性和灵敏度。在单层细胞和三维多细胞球体中评估了Mito-SeH的低氧反应行为，以阐明亚砜硫与低氧之间的关系。我们证实，硫磺对缺氧的保护机制是通过直接清除ROS途径来抑制caspase依赖性细胞凋亡。该探针还用于测量缺氧小鼠模型的离体解剖器官中的亚砜硫，以及该探针已成功用于实时监测急性缺血小鼠模型中硫丹和ROS的变化。我们建议，硫磺硫可能是一种新的缺氧诱导的损伤的治疗剂。
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