Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Redox Biol. 2019 Jan;20:526-532. doi: 10.1016/j.redox.2018.11.011. Epub 2018 Nov 22.
Intestinal homeostasis is regulated in-part by reactive oxygen species (ROS) that are generated in the colonic mucosa following contact with certain lactobacilli. Mechanistically, ROS can modulate protein function through the oxidation of cysteine residues within proteins. Recent advances in cysteine labeling by the Isotope Coded Affinity Tags (ICATs) technique has facilitated the identification of cysteine thiol modifications in response to stimuli. Here, we used ICATs to map the redox protein network oxidized upon initial contact of the colonic mucosa with Lactobacillus rhamnosus GG (LGG). We detected significant LGG-specific redox changes in over 450 proteins, many of which are implicated to function in cellular processes such as endosomal trafficking, epithelial cell junctions, barrier integrity, and cytoskeleton maintenance and formation. We particularly noted the LGG-specific oxidation of Rac1, which is a pleiotropic regulator of many cellular processes. Together, these data reveal new insights into lactobacilli-induced and redox-dependent networks involved in intestinal homeostasis.
肠道内环境的稳定部分受到活性氧（ROS）的调控，这些 ROS 是在与某些乳杆菌接触后，在结肠黏膜中产生的。从机制上讲，ROS 可以通过氧化蛋白质中的半胱氨酸残基来调节蛋白质的功能。最近，通过同位素编码亲和标签（ICATs）技术对半胱氨酸进行标记的进展，促进了对刺激响应的半胱氨酸巯基修饰的鉴定。在这里，我们使用 ICATs 来绘制在结肠黏膜与鼠李糖乳杆菌 GG（LGG）最初接触时被氧化的氧化还原蛋白网络。我们检测到超过 450 种蛋白质的 LGG 特异性氧化还原变化，其中许多蛋白质与细胞过程有关，如内体运输、上皮细胞连接、屏障完整性以及细胞骨架的维持和形成。我们特别注意到 Rac1 的 LGG 特异性氧化，Rac1 是许多细胞过程的多效调节剂。总之，这些数据揭示了与肠道内环境稳定相关的乳杆菌诱导和氧化还原依赖性网络的新见解。
