Romero Juan Ignacio, Hanschmann Eva-Maria, Gellert Manuela, Eitner Susanne, Holubiec Mariana Inés, Blanco-Calvo Eduardo, Lillig Christopher Horst, Capani Francisco
Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), Facultad de Medicina, UBA-CONICET, Marcelo T. de Alvear 2270, C1122AAJ, Ciudad de Buenos Aires, Argentina.
Institute for Medical Biochemistry and Molecular Biology, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt-Universität Greifswald, 17475 Greifswald, Germany.
Biochim Biophys Acta. 2015 Jun;1850(6):1274-85. doi: 10.1016/j.bbagen.2015.02.015. Epub 2015 Feb 28.
Thioredoxin (Trx) family proteins are crucial mediators of cell functions via regulation of the thiol redox state of various key proteins and the levels of the intracellular second messenger hydrogen peroxide. Their expression, localization and functions are altered in various pathologies. Here, we have analyzed the impact of Trx family proteins in neuronal development and recovery, following hypoxia/ischemia and reperfusion.
We have analyzed the regulation and potential functions of Trx family proteins during hypoxia/ischemia and reoxygenation of the developing brain in both an animal and a cellular model of perinatal asphyxia. We have analyzed the distribution of 14 Trx family and related proteins in the cerebellum, striatum, and hippocampus, three areas of the rat brain that are especially susceptible to hypoxia. Using SH-SY5Y cells subjected to hypoxia and reoxygenation, we have analyzed the functions of some redoxins suggested by the animal experiment.
We have described/discovered a complex, cell-type and tissue-specific expression pattern following the hypoxia/ischemia and reoxygenation. Particularly, Grx2 and Trx1 showed distinct changes during tissue recovery following hypoxia/ischemia and reoxygenation. Silencing of these proteins in SH-SY5Y cells subjected to hypoxia-reoxygenation confirmed that these proteins are required to maintain the normal neuronal phenotype.
These findings demonstrate the significance of redox signaling in cellular pathways. Grx2 and Trx1 contribute significantly to neuronal integrity and could be clinically relevant in neuronal damage following perinatal asphyxia and other neuronal disorders.
硫氧还蛋白（Trx）家族蛋白通过调节各种关键蛋白的硫醇氧化还原状态以及细胞内第二信使过氧化氢的水平，成为细胞功能的关键调节因子。它们的表达、定位和功能在各种病理状态下会发生改变。在此，我们分析了Trx家族蛋白在缺氧/缺血及再灌注后对神经元发育和恢复的影响。
我们在围产期窒息的动物模型和细胞模型中，分析了发育中大脑在缺氧/缺血及复氧过程中Trx家族蛋白的调节及其潜在功能。我们分析了14种Trx家族及相关蛋白在小脑、纹状体和海马体中的分布，这三个脑区是大鼠脑中对缺氧特别敏感的区域。利用经缺氧和复氧处理的SH-SY5Y细胞，我们分析了动物实验中提示的一些氧化还原蛋白的功能。
我们描述/发现了缺氧/缺血及复氧后一种复杂的、细胞类型和组织特异性的表达模式。特别是，谷氧还蛋白2（Grx2）和硫氧还蛋白1（Trx1）在缺氧/缺血及复氧后的组织恢复过程中表现出明显变化。在经缺氧-复氧处理的SH-SY5Y细胞中沉默这些蛋白，证实这些蛋白是维持正常神经元表型所必需的。
这些发现证明了氧化还原信号在细胞通路中的重要性。Grx2和Trx1对神经元完整性有显著贡献，在围产期窒息及其他神经元疾病后的神经元损伤中可能具有临床相关性。
