Itakura Yoko, Sasaki Norihiko, Toyoda Masashi
Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
Aging (Albany NY). 2018 Aug 29;10(8):2190-2208. doi: 10.18632/aging.101540.
Glycans are associated with and serve as biomarkers for various biological functions. We previously reported that cell surface sialylated glycoproteins of dermal fibroblasts decreased with cellular senescence and human aging. There is little information on the changes in glycoprotein expression and subcellular localization during the aging process. Here, we examined intracellular glycan profiles of fibroblasts undergoing cellular senescence and those derived from aging human subjects using lectin microarray analysis. We found a sequential change of the intracellular glycan profiles was little during cellular senescence. The intracellular glycans of cells derived from aged fetus and from elderly subjects showed similar localized patterns while repeating unsteady changes. The ratio of α2-3/2-6sialylated intracellular glycoproteins in total cell extracts increased, except for a part of α2-3sialylated -glycans. These findings are in contrast to those for membrane glycoprotein, which decreased with aging. Interestingly, the ratio of increasing sialylated glycoproteins in the fetus-derived cells showing cellular senescence was similar to that in cells derived from the elderly. Thus, intracellular glycans may maintain cellular functions such as ubiquitin/proteasome-mediated degradation and/or autophagy during aging by contributing to the accumulation of intracellular glycosylated proteins. Our findings provide novel mechanistic insight into the molecular changes that occur during aging.
聚糖与多种生物学功能相关，并作为其生物标志物。我们之前报道过，真皮成纤维细胞的细胞表面唾液酸化糖蛋白会随着细胞衰老和人类老化而减少。关于衰老过程中糖蛋白表达和亚细胞定位的变化，目前所知甚少。在此，我们使用凝集素微阵列分析，研究了经历细胞衰老的成纤维细胞以及来自老年人类受试者的成纤维细胞的细胞内聚糖谱。我们发现，在细胞衰老过程中，细胞内聚糖谱的顺序变化很小。来自老年胎儿和老年受试者的细胞的细胞内聚糖呈现出相似的定位模式，同时伴有不稳定的变化。除了一部分α2-3唾液酸化聚糖外，总细胞提取物中α2-3/2-6唾液酸化细胞内糖蛋白的比例增加。这些发现与膜糖蛋白的情况相反，膜糖蛋白会随着衰老而减少。有趣的是，呈现细胞衰老的胎儿来源细胞中唾液酸化糖蛋白增加的比例与老年受试者来源细胞中的比例相似。因此，细胞内聚糖可能通过促进细胞内糖基化蛋白的积累，在衰老过程中维持细胞功能，如泛素/蛋白酶体介导的降解和/或自噬。我们的发现为衰老过程中发生的分子变化提供了新的机制性见解。
