Turovsky Egor A, Plotnikov Egor Y, Varlamova Elena G
Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", 142290 Pushchino, Russia.
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Biomedicines. 2024 Aug 5;12(8):1756. doi: 10.3390/biomedicines12081756.
Despite the successes in the prevention and treatment of strokes, it is still necessary to search for effective cytoprotectors that can suppress the damaging factors of cerebral ischemia. Among the known neuroprotectors, there are a number of drugs with a protein nature. In the present study, we were able to obtain recombinant SELENOM, a resident of the endoplasmic reticulum that exhibits antioxidant properties in its structure and functions. The resulting SELENOM was tested in two brain injury (in vitro) models: under ischemia-like conditions (oxygen-glucose deprivation/reoxygenation, OGD/R) and glutamate excitotoxicity (GluTox). Using molecular biology methods, fluorescence microscopy, and immunocytochemistry, recombinant SELENOM was shown to dose-dependently suppress ROS production in cortical cells in toxic models, reduce the global increase in cytosolic calcium ([Ca]), and suppress necrosis and late stages of apoptosis. Activation of SELENOM's cytoprotective properties occurs due to its penetration into cortical cells through actin-dependent transport and activation of the Ca signaling system. The use of SELENOM resulted in increased antioxidant protection of cortical cells and suppression of the proinflammatory factors and cytokines expression.
尽管在中风的预防和治疗方面取得了成功，但仍有必要寻找能够抑制脑缺血损伤因素的有效细胞保护剂。在已知的神经保护剂中，有许多具有蛋白质性质的药物。在本研究中，我们成功获得了重组硒蛋白M（SELENOM），它是一种内质网驻留蛋白，在结构和功能上具有抗氧化特性。将所得的SELENOM在两种脑损伤（体外）模型中进行测试：在类缺血条件下（氧糖剥夺/复氧，OGD/R）和谷氨酸兴奋性毒性（GluTox）模型。使用分子生物学方法、荧光显微镜和免疫细胞化学技术，结果表明重组SELENOM在毒性模型中能剂量依赖性地抑制皮质细胞中活性氧的产生，降低胞质钙（[Ca]）的整体升高，并抑制坏死和凋亡的晚期阶段。SELENOM细胞保护特性的激活是由于其通过肌动蛋白依赖性转运进入皮质细胞并激活钙信号系统。使用SELENOM可增强皮质细胞的抗氧化保护作用，并抑制促炎因子和细胞因子的表达。
