利用微阵列技术深入了解甲基丙二酸血症的分子机制。
Insights into the molecular mechanisms of methylmalonic acidemia using microarray technology.
作者信息
Han Lianshu, Wu Shengnan, Han Feng, Gu Xuefan
机构信息
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine Shanghai 200092, China.
出版信息
Int J Clin Exp Med. 2015 Jun 15;8(6):8866-79. eCollection 2015.
Abstract
Methylmalonic acidemia (MMA) is widely considered as an autosomal recessive metabolic disorder that results in accumulation of high levels of methylmalonic acid and eventually brain damage. This study aims to investigate the effects of methylmalonic acid on neurons and analyze various gene expression profiles in rat cortical neurons treated with methylmalonic acid in order to understand the effects of MMA. High concentrations of methylmalonic acid could significantly alter the morphology of rat cortical neurons, attenuate cell viability and aggravate cell apoptosis. Moreover, 564 differentially expressed genes were identified by microarray analysis. A considerable number of these genes were apoptosis-related genes. Enrichment analysis of the apoptosis-related genes revealed that the MAPK and p53 signaling pathways may be involved in the pathogenesis of MMA. Our results together reveal that methylmalonic acid plays a critical role in neuron damage and that the MAPK and p53 signaling pathways may be involved in the mechanism of MMA.
摘要
甲基丙二酸血症（MMA）被广泛认为是一种常染色体隐性代谢紊乱疾病，会导致高水平甲基丙二酸的积累，并最终造成脑损伤。本研究旨在探究甲基丙二酸对神经元的影响，并分析用甲基丙二酸处理的大鼠皮质神经元中的各种基因表达谱，以了解MMA的作用机制。高浓度的甲基丙二酸可显著改变大鼠皮质神经元的形态，降低细胞活力并加剧细胞凋亡。此外，通过微阵列分析鉴定出564个差异表达基因。其中相当一部分基因是凋亡相关基因。对凋亡相关基因的富集分析表明，丝裂原活化蛋白激酶（MAPK）和p53信号通路可能参与了MMA的发病机制。我们的研究结果共同表明，甲基丙二酸在神经元损伤中起关键作用，并且MAPK和p53信号通路可能参与了MMA的发病机制。
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