Abstract
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 O-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.
Highlights
In vitro-senescent cells are characterized by morphological changes, proliferation arrest, decreased electrophoretic mobility, and telomere shortening [1,2,3]
We investigated the changes in intracellular glycan profiles during cellular senescence and human aging by lectin microarray analysis using TIG human skin fibroblast lines [10]
To investigate intracellular glycan profiles associated with population doubling level (PDL) in fibroblasts derived from fetus (TIG-3S) and elderly subjects (TIG101 and TIG-102, from 86- and 97-year-old subjects, respectively), a lectin microarray analysis was carried out in the same manner as for our previous membrane glycan profile analysis [10]
Summary
In vitro-senescent cells are characterized by morphological changes, proliferation arrest, decreased electrophoretic mobility, and telomere shortening [1,2,3]. Senescent cells exhibit negative or positive effects such as functional disruption, hyperplasia, tumor suppression, and immune facilitation [4]. For longterm maintenance of normal biological functions, it is important to clarify protein dynamics in cells during the processes of cellular senescence and human aging. Expression of the cell surface glycosphingolipid monosialotetrahexosyl-ganglioside (GM1) was shown to increase with cellular senescence in human aortic endothelial cells [9], whereas the cell surface sialic acid level of glycoprotein was decreased in human dermal fibroblasts [10]. The sialic acid species was identified as α2-3sialylated Oglycan; in human aging cells, the species was α2-3/α26sialylated N-/O-glycan. The above-mentioned reduction was associated with activation of fibrogenesis in human skin fibroblasts [11]
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