Miura Yuri, Tsumoto Hiroki, Masui Yukie, Inagaki Hiroki, Ogawa Madoka, Ideno Yuta, Kawakami Kyojiro, Umezawa Keitaro, Kabayama Mai, Akagi Yuya, Akasaka Hiroshi, Yamamoto Koichi, Rakugi Hiromi, Ishizaki Tatsuro, Arai Yasumichi, Ikebe Kazunori, Kamide Kei, Gondo Yasuyuki, Endo Tamao
Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
Biochim Biophys Acta Gen Subj. 2023 Apr;1867(4):130316. doi: 10.1016/j.bbagen.2023.130316. Epub 2023 Jan 30.
Identifying a biomarker for the decline in cognitive function in patients with diabetes is important. Therefore, we aimed to identify the N-glycopeptides on plasma proteins associated with diabetic cognitive impairment in participants in a longitudinal study using N-glycoproteomics.
We used samples from the 3-year SONIC (Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians) longitudinal cohort study of older Japanese people in the general population. First, we placed the participants with diabetes into two groups: those that did or did not have cognitive decline over a 6-year period. Next, their plasma protein profiles were compared between baseline and the 6-year time point using two-dimensional fluorescence difference gel electrophoresis. Finally, an N-glycoproteomic study of the focused proteins was performed using an enrichment technique and liquid chromatography-tandem mass spectrometry.
Approximately 500 N-glycopeptides, derived from 18 proteins, were identified in each sample, from among which we identified the N-glycopeptides that were associated with diabetic cognitive impairment using multivariate analysis. We found that N-glycopeptides with sialylated tri- or tetra-antennary glycans on alpha-2-macroglobulin, clusterin, serum paraoxonase/arylesterase 1, and haptoglobin were less abundant, whereas 3-sialylated tri-antennary N-glycopeptides on serotransferrin were more abundant.
N-glycopeptides with sialylated multi-antennary glycans comprise a characteristic signature associated with diabetic cognitive impairment.
The characterized N-glycopeptides represent potential biomarker candidates for diabetic cognitive impairment.
识别糖尿病患者认知功能下降的生物标志物很重要。因此，我们旨在通过N-糖蛋白质组学在一项纵向研究的参与者中识别与糖尿病性认知障碍相关的血浆蛋白上的N-糖肽。
我们使用了对普通人群中日本老年人进行的为期3年的SONIC（七十、八十、九十、百岁老人调查）纵向队列研究的样本。首先，我们将糖尿病参与者分为两组：在6年期间有或没有认知功能下降的参与者。接下来，使用二维荧光差异凝胶电泳比较他们在基线和6年时间点的血浆蛋白谱。最后，使用富集技术和液相色谱-串联质谱对重点蛋白质进行N-糖蛋白质组学研究。
每个样本中鉴定出约500种源自18种蛋白质的N-糖肽，我们通过多变量分析从中鉴定出与糖尿病性认知障碍相关的N-糖肽。我们发现，α-2-巨球蛋白、簇蛋白、血清对氧磷酶/芳基酯酶1和触珠蛋白上具有唾液酸化三或四天线聚糖的N-糖肽含量较低，而血清转铁蛋白上3-唾液酸化三天线N-糖肽含量较高。
具有唾液酸化多天线聚糖的N-糖肽构成了与糖尿病性认知障碍相关的特征性标志。
所表征的N-糖肽代表糖尿病性认知障碍的潜在生物标志物候选物。
