Characteristic glycopeptides associated with extreme human longevity identified through plasma glycoproteomics
Characteristic glycopeptides associated with extreme human longevity identified through plasma glycoproteomics
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DOI：
10.1016/j.bbagen.2018.03.025
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发表时间：
2018-06-01
影响因子：
3
通讯作者：
Endo, Tamao
中科院分区：
文献类型：
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作者：
Miura, Yuri;Hashii, Noritaka;Endo, Tamao
背景资料：糖基化对生理条件的变化高度敏感，因此，是与几种疾病和/或长寿相关的潜在生物标志物。半超百岁老人（Semi-supercentenarians，SSC）被认为是人类长寿的典范。因此，我们进行糖蛋白质组学使用血浆样本的精原细胞，并确定蛋白质和共轭N-聚糖的特点是极端的人类longevison.Methods：血浆蛋白从日本半supercentenarians（精原细胞，106-109年），老年对照（70-88岁），和年轻的对照（20-38岁）进行了分析，通过使用凝集素微阵列和液相色谱/质谱（LC/MS）。对糖肽与相应标准化肽的峰面积比进行正交投影潜在结构判别分析（OPLS-DA）。此外，血浆水平的临床生物标志物measured.Results：我们发现两个凝集素，如菜豆，和刺桐（ECA），其中蛋白结合的特征性增加在精原干细胞。使用OPLS-DA成功区分SSC和对照之间的ECA富集的糖肽的峰面积比，并表明在SSC中表征了Asn 207和Asn 211位点处的触珠蛋白的三触角和唾液酸化N-聚糖。结合珠蛋白的唾液酸化聚糖是几种疾病的潜在生物标志物，例如肝细胞癌、肝硬化和IgA肾炎。然而，这里分析的精原细胞没有遭受这些diseases.Conclusions：三触角和唾液酸化的N-聚糖的结合珠蛋白在Asn 207和Asn 211网站是丰富的精原细胞和特征的极端人类长寿。一般意义：我们在SSC中发现了丰富的聚糖，这可能与人类长寿有关。
Background: Glycosylation is highly susceptible to changes of the physiological conditions, and accordingly, is a potential biomarker associated with several diseases and/or longevity. Semi-supercentenarians (SSCs; older than 105 years) are thought to be a model of human longevity. Thus, we performed glycoproteomics using plasma samples of SSCs, and identified proteins and conjugated N-glycans that are characteristic of extreme human longevity.Methods: Plasma proteins from Japanese semi-supercentenarians (SSCs, 106-109 years), aged controls (70-88 years), and young controls (20-38 years) were analysed by using lectin microarrays and liquid chromatography/mass spectrometry (LC/MS). Peak area ratios of glycopeptides to corresponding normalising peptides were subjected to orthogonal projections to latent structures discriminant analysis (OPLS-DA). Furthermore, plasma levels of clinical biomarkers were measured.Results: We found two lectins such as Phaseolus vulgaris, and Erythrina cristagalli (ECA), of which protein binding were characteristically increased in SSCs. Peak area ratios of ECA-enriched glycopeptides were successfully discriminated between SSCs and controls using OPLS-DA, and indicated that tri-antennary and sialylated N-glycans of haptoglobin at Asn207 and Asn211 sites were characterized in SSCs. Sialylated glycans of haptoglobin are a potential biomarker of several diseases, such as hepatocellular carcinoma, liver cirrhosis, and IgA-nephritis. However, the SSCs analysed here did not suffer from these diseases.Conclusions: Tri-antennary and sialylated N-glycans on haptoglobin at the Asn207 and Asn211 sites were abundant in SSCs and characteristic of extreme human longevity. General significance: We found abundant glycans in SSCs, which may be associated with human longevity.