Age-related increase of prostaglandin D2 synthase concentration and glycation in ovine cerebrospinal fluid
Age-related increase of prostaglandin D2 synthase concentration and glycation in ovine cerebrospinal fluid
复制标题
DOI：
10.1016/j.exger.2009.07.001
复制
发表时间：
2009-10-01
影响因子：
3.9
通讯作者：
Preston, Jane E.
中科院分区：
文献类型：
--
作者：
Chen, Carl P. C.;Chen, Ruo Li;Preston, Jane E.
前列腺素D-2合成酶(PGDS)是一种脑源性糖蛋白，是脑脊液中含量最丰富的蛋白质之一。由于其高度的脑脊液特异性，它可以作为诊断中枢神经系统(CNS)疾病的工具。然而，几项研究发现，在不同的中枢神经退行性疾病中，脑脊液中PGDS的浓度相互矛盾。本研究以不同年龄的绵羊脑脊液为材料，采用双向凝胶电泳法(2-DE)进行PGDS的鉴定和浓度计算。SYPRO红宝石蛋白凝胶染色是2-DE凝胶蛋白斑点的染色方法。Pro-Q Emerald 488糖蛋白染色用于糖蛋白染色。共鉴定出9种PGDS亚型，并计算出脑脊液总PGDS浓度从青年(0.9323+/-0.0637 mg dL(-1))到老年(1.3669+/-0.0558 mg dL(-1))线性增加44%。然而，脑脊液总PGDS占脑脊液总蛋白的比例随年龄的增长呈指数下降。这是由于脑脊液白蛋白浓度随年龄增加(从年轻到老年增加200%)的影响，因为白蛋白是脑脊液中含量最丰富的蛋白质(占总脑脊液蛋白的60%)。在健康的衰老过程中，没有观察到PGDS亚型的主动脱糖作用。观察到一些PGDS亚型具有与年龄相关的糖基化增加。这些发现表明，在健康的衰老过程中，脑脊液中PGDS的浓度会增加，当使用PGDS作为诊断中枢神经退行性疾病的潜在生物标志物时，必须考虑到这一点。某些脑脊液PGDS亚型糖基化水平的增龄性增加是否会对PGDS蛋白功能产生不利影响还有待进一步研究。(C)2009 Elsevier Inc.保留所有权利。
Prostaglandin D-2 synthase (PGDS) is a glycoprotein that is exclusively brain derived and is one of the most abundant proteins in the cerebrospinal fluid (CSF). Due to its high CSF specificity, it can be used as a tool for the diagnosis of central nervous system (CNS) disorders. However, several studies have yielded contradictory CSF PGDS concentrations in various CNS neurodegenerative disorders. Sheep CSF samples from different ages were used in this study and 2-dimensional electrophoresis (2-DE) was applied in PGDS identification and concentration calculation. SYPRO Ruby Protein Gel Stain was the staining method used to stain the 2-DE gel protein spots. Pro-Q Emerald 488 Staining for Glycoproteins was used for the staining of glycoproteins. A total of nine PGDS isoforms were identified and CSF total PGDS concentration was calculated to increase linearly by 44% from young (0.9323 +/- 0.0637 mg dL(-1)) to old (1.3669 +/- 0.0558 mg dL(-1)). However, the proportion of CSF total PGDS as a percentage of CSF total protein was discovered to decrease exponentially with age. This was due to the influence of larger age-related increase in CSF albumin concentration (>200% from young to old) as albumin is the most abundant protein in the CSF (>60% of total CSF proteins). Active deglycosylation was not observed in PGDS isoforms during healthy ageing. Some PGDS isoforms were observed to have age-related increase in glycation. These findings suggest that CSF PGDS concentration is increased during healthy ageing and must be taken into consideration when using PGDS as a potential biomarker in diagnosing CNS neurodegenerative disorders. Whether age-related increase in the glycation of some CSF PGDS isoforms will result in detrimental effects on the PGDS protein function needs further investigations. (C) 2009 Elsevier Inc. All rights reserved.