Vigont V A, Zimina O A, Glushankova L N, Kolobkova J A, Ryazantseva M A, Mozhayeva G N, Kaznacheyeva E V
Institute of Cytology, Russian Academy of Sciences, Tikhoretsky pr., 4, St. Petersburg, 194064, Russia.
Acta Naturae. 2014 Oct;6(4):40-7.
We have shown that the expression of full-length mutated huntingtin in human neuroblastoma cells (SK-N-SH) leads to an abnormal increase in calcium entry through store-operated channels. In this paper, the expression of the N-terminal fragment of mutated huntingtin (Htt138Q-1exon) is shown to be enough to provide an actual model for Huntington's disease. We have shown that Htt138Q-1exon expression causes increased store-operated calcium entry, which is mediated by at least two types of channels in SK-N-SH cells with different reversal potentials. Calcium sensor, STIM1, is required for activation of store-operated calcium entry in these cells. The results provide grounds for considering the proteins responsible for the activation and maintenance of the store-operated calcium entry as promising targets for developing novel therapeutics for neurodegenerative diseases.
我们已经表明，在人神经母细胞瘤细胞（SK-N-SH）中全长突变型亨廷顿蛋白的表达会导致通过储存操纵性通道的钙内流异常增加。在本文中，突变型亨廷顿蛋白N端片段（Htt138Q-1exon）的表达被证明足以提供一个亨廷顿病的实际模型。我们已经表明，Htt138Q-1exon的表达会导致储存操纵性钙内流增加，这是由SK-N-SH细胞中至少两种具有不同反转电位的通道介导的。钙传感器STIM1是这些细胞中储存操纵性钙内流激活所必需的。这些结果为将负责储存操纵性钙内流激活和维持的蛋白质视为开发神经退行性疾病新疗法的有前景靶点提供了依据。
