Altered plasma protein glycosylation in a mouse model of depression and in patients with major depression
Altered plasma protein glycosylation in a mouse model of depression and in patients with major depression
复制标题
抑郁症小鼠模型和重度抑郁症患者血浆蛋白糖基化的改变
DOI：
10.1016/j.jad.2017.08.057
复制
发表时间：
2018
影响因子：
6.6
通讯作者：
Watanabe Yoshifumi
中科院分区：
文献类型：
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作者：
Yamagata Hirotaka;Uchida Shusaku;Matsuo Koji;Harada Kenichiro;Kobayashi Ayumi;Nakashima Mami;Higuchi Fumihiro;Watanuki Toshio;Matsubara Toshio;Watanabe Yoshifumi
背景糖基化是蛋白质生物合成中常见的翻译后修饰，与多种疾病状态有关。据报道，特定的蛋白聚糖结构可用作癌症和一些神经精神疾病的生物标志物；然而，血浆蛋白糖基化与重度抑郁症（MDD）之间的关系迄今为止尚未得到研究。本研究的目的是使用基于压力的小鼠模型和来自 MDD 患者的样本来确定血浆蛋白聚糖结构是否在抑郁症中发生改变。方法我们使用未经治疗或接受丙咪嗪治疗的慢性超轻度压力小鼠分别作为抑郁症和缓解小鼠模型。我们还对抑郁症和缓解期重度抑郁症患者的样本进行了比较。使用凝集素微阵列分析蛋白质糖基化，该微阵列包括 45 种对各种聚糖结构具有结合亲和力的凝集素。结果Sia-alpha2-6Gal/GalNAc 是抑郁症模型小鼠和 MDD 患者中常见的改变的聚糖结构。此外，MDD患者白细胞中ST6GALNAC2的表达降低。局限性我们的研究样本较小，我们没有鉴定出特异性的α2-6Gal/GalNAc唾液酸化蛋白。结论血浆蛋白中的聚糖结构Sia-α2-6GalNAc和外周白细胞中ST6GALNAC2的表达可能具有实用性 作为 MDD 临床诊断和监测的候选生物标志物。
BackgroundGlycosylation is a common posttranslational modification in protein biosynthesis that is implicated in several disease states. It has been reported that specific protein glycan structures are useful as biomarkers for cancer and some neuropsychiatric diseases; however, the relationship between plasma protein glycosylation and major depressive disorder (MDD) has not been investigated to date. The aim of this study was to determine whether plasma protein glycan structures are altered in depression using a stress-based mouse model and samples from patients with MDD.MethodsWe used chronic ultra-mildly stressed mice that were untreated or treated with imipramine as mouse models of depression and remission, respectively. We also made comparisons between samples from depressed and remitted patients with MDD. Protein glycosylation was analyzed using a lectin microarray that included 45 lectins with binding affinities for various glycan structures.ResultsSia-alpha2-6Gal/GalNAc was a commonly altered glycan structure in both depression model mice and patients with MDD. Moreover, the expression of ST6GALNAC2 was decreased in leukocytes from patients with MDD.LimitationsOur study samples were small and we did not identify specific alpha2-6Gal/GalNAc-sialylated proteins.ConclusionsThe glycan structure Sia-alpha2-6GalNAc in plasma protein and ST6GALNAC2 expression in peripheral leukocytes may have utility as candidate biomarkers for the clinical diagnosis and monitoring of MDD.