Beta-Catenin and SMAD3 Are Associated with Skeletal Muscle Aging in the Taurine Transpoeter Knockout Mouse
Beta-Catenin and SMAD3 Are Associated with Skeletal Muscle Aging in the Taurine Transpoeter Knockout Mouse
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DOI：
10.1007/978-94-024-1079-2_39
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发表时间：
2017-01-01
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影响因子：
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通讯作者：
Schaffer, Stephen W.
中科院分区：
文献类型：
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作者：
Ito, Takashi;Yamamoto, Nao;Schaffer, Stephen W.
通过敲除牛磺酸转运蛋白介导的组织牛磺酸耗竭导致几种骨骼肌异常，包括细胞老化加速。在本研究中，我们研究了参与加速骨骼肌衰老的组织牛磺酸消耗的转录组数据的生物信息学方法的信号通路。我们先前使用DNA微阵列对牛磺酸转运蛋白基因敲除（TauTKO）小鼠的骨骼肌进行转录组分析。转录组数据的生物信息学分析预测SMAD 3和β-连环蛋白作为细胞周期蛋白依赖性激酶抑制剂2A（CDKN 2A，也称为p16 INK 4A）的上游信号分子的激活，CDKN 2A是细胞衰老的生物标志物基因。SMAD 3和β-连环蛋白在老TauTKO肌肉中的活化通过蛋白质印迹分析验证。这些数据表明SMAD 3和β-连环蛋白依赖性诱导发生在TauTKO小鼠中。
Tissue taurine depletion mediated by knocking out the taurine transporter causes several skeletal muscle abnormalities, including acceleration of cellular aging. In the present study, we investigated the signaling pathway involved in the acceleration of skeletal muscle aging by tissue taurine depletion using the bioinformatic approach of transcriptome data. We previously performed transcriptome analysis on skeletal muscle of taurine transporter knockout (TauTKO) mice using DNA microarray. Bioinformatic analysis of transcriptome data predicted the activation of SMAD3 and beta-catenin as upstream signaling molecules of cyclin-dependent kinase inhibitor 2A (CDKN2A, also called p16INK4A), which is a biomarker gene of cellular senescence. The activation of SMAD3 and beta-catenin in old TauTKO muscle was verified by western blot analysis. These data indicate that SMAD3- and beta-catenin-dependent induction occurs in the TauTKO mouse.