Kinoshita Mitsuhiro, Yamamoto Sachio, Suzuki Shigeo
Faculty of Pharmaceutical Sciences, Kindai University, Kowakae 3-4-1, Higashi-osaka 577-8502, Japan.
ACS Omega. 2020 Jul 16;5(30):18608-18618. doi: 10.1021/acsomega.0c00935. eCollection 2020 Aug 4.
O-Acetylation of sialic acids has been widely found in eukaryotic cells. Such modifications of sialic acids are tissue-specific and seem to be developmentally regulated. In this study, we performed comprehensive analysis of age-related changes in the serum N-glycans of male rats using capillary electrophoresis (CE) and investigated the changes in the O-acetylation of sialic acids bound to N-glycans with aging and different diets. The present method offered sufficient resolution to assess the degree of O-acetylation of the N-glycans and allowed for the determination of the age-related changes in O-acetylation of sialic acids. Using the CE-based method, we found that the relative abundance of disialo-biantennary N-glycans modified with 9-O-acetylated -acetylneuraminic acid (Neu5,9Ac) significantly increased with aging. In addition, the relative abundances of N-glycans with two Neu5,9Ac reversed to those of N-glycans with only Neu5Ac during 12 weeks. Next, we evaluated the influence of high-fat diet and food restriction on age-related changes in O-acetylation. Although the total amount of disialo-biantennary N-glycans increased with aging, age-related O-acetylation of sialic acids was suppressed by a high-fat diet. On the other hand, food restriction enhanced the O-acetylation of sialic acids, and the relative abundance of N-glycans with two Neu5,9Ac residues at 15 weeks of age was higher than that observed in the standard diet group. These findings suggest that the O-acetylation of sialic acids is closely related to changes in energy metabolisms such as glycolysis or fatty acid metabolism.
唾液酸的O-乙酰化在真核细胞中广泛存在。唾液酸的这种修饰具有组织特异性,且似乎受发育调控。在本研究中,我们使用毛细管电泳(CE)对雄性大鼠血清N-聚糖的年龄相关变化进行了全面分析,并研究了与N-聚糖结合的唾液酸O-乙酰化随衰老和不同饮食的变化。本方法提供了足够的分辨率来评估N-聚糖的O-乙酰化程度,并能够测定唾液酸O-乙酰化的年龄相关变化。使用基于CE的方法,我们发现用9-O-乙酰化-α-乙酰神经氨酸(Neu5,9Ac)修饰的二唾液酸-双天线N-聚糖的相对丰度随衰老显著增加。此外,在12周内,具有两个Neu5,9Ac的N-聚糖的相对丰度与仅具有Neu5Ac的N-聚糖的相对丰度发生了逆转。接下来,我们评估了高脂饮食和食物限制对O-乙酰化年龄相关变化的影响。尽管二唾液酸-双天线N-聚糖的总量随衰老增加,但高脂饮食抑制了唾液酸的年龄相关O-乙酰化。另一方面,食物限制增强了唾液酸的O-乙酰化,并且在15周龄时具有两个Neu5,9Ac残基的N-聚糖的相对丰度高于标准饮食组。这些发现表明,唾液酸的O-乙酰化与糖酵解或脂肪酸代谢等能量代谢变化密切相关。