Age-related accumulation of pentosidine in aggrecan and collagen from normal and degenerate human intervertebral discs
Age-related accumulation of pentosidine in aggrecan and collagen from normal and degenerate human intervertebral discs
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DOI：
10.1042/bj20060579
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发表时间：
2006-10-01
影响因子：
4.1
通讯作者：
Maroudas, Alice
中科院分区：
文献类型：
--
作者：
Sivan, Sarit Sara;Tsitron, Eve;Maroudas, Alice
在衰老和退化过程中，人体软骨组织的结构和成分会发生许多变化，其中包括 AGE（晚期糖基化终产物）、戊糖苷在长寿蛋白中的积累。在本研究中，我们研究了健康和病理状态下人体 IVD（椎间盘）成分中戊糖素的积累，即胶原蛋白、聚集蛋白聚糖衍生的 PG（蛋白聚糖）(A1) 及其组分 (A1D1-A1D6)。我们发现，成熟后，戊糖素会随着年龄的增长而积累。在研究的年龄范围内，观察到 A1 和胶原蛋白的戊糖素积累线性增加 6 倍，分别为 0.12 和 0.66 nmol (.) (g 蛋白质)(-1) (.) 年(-1)。使用先前报道的从人类 IVD 的胶原蛋白和聚集蛋白聚糖中天冬氨酸残基的 D-异构体测量中获得的蛋白质周转率常数 (k(T))，我们可以计算这些成分的戊糖苷形成率常数 (k(F)) [Sivan, Tsitron, Wachtel, Roughley, Sakkee, van der Ham, DeGroot, Roberts 和 Maroudas (2006) J. Biol.化学。 281、13009-13014； Tsitron (2006) 硕士论文，以色列理工学院，以色列海法]。尽管 A1D1 和胶原蛋白的形成速率常数相当[分别为 1.81 +/- 0.25 与 3.71 +/- 0.26 mu mol 戊糖苷 (.) (摩尔赖氨酸)(-1) (.) 年(-1)]，胶原蛋白中较高的戊糖苷积累与其较慢的周转率一致（0.005 年(-1) 与 0.134 年(-1) 相比） A1D1）。随着浮力密度的降低和蛋白质周转率的降低，戊糖胺积累量增加，从最富含糖胺聚糖的PG成分(A1D1)到最少的(A1D6)，相应的k(F)值为1.81+/-0.25和3.18+/-0.37μmol戊糖胺(.)(mol赖氨酸)(-1)(.)年(-1)。我们得出的结论是，正如在关节软骨中所发现的那样，蛋白质周转是人 IVD 的聚集蛋白聚糖和胶原蛋白中戊糖素积累的重要决定因素。正常和退化椎间盘中戊糖素积累与蛋白质半衰期的相关性进一步支持了这一发现。
During aging and degeneration, many changes occur in the structure and composition of human cartilaginous tissues, which include the accumulation of the AGE (advanced glycation end-product), pentosidine, in long-lived proteins. In the present study, we investigated the accumulation of pentosidine in constituents of the human IVD (intervertebral disc), i.e. collagen, aggrecan-derived PG (proteoglycan) (A1) and its fractions (A1D1-A1D6) in health and pathology. We found that, after maturity, pentosidine accumulates with age. Over the age range studied, a linear 6-fold increase was observed in pentosidine accumulation for A1 and collagen with respective rates of 0.12 and 0.66 nmol (.) (g of protein)(-1) (.) year(-1). Using previously reported protein turnover rate constants (k(T)) obtained from measurements of the D-isomer of aspartic residue in collagen and aggrecan of human IVD, we could calculate the pentosidine formation rate constants (k(F)) for these constituents [Sivan, Tsitron, Wachtel, Roughley, Sakkee, van der Ham, DeGroot, Roberts and Maroudas (2006) J. Biol. Chem. 281, 13009-13014; Tsitron (2006) MSc Thesis, Technion-Israel Institute of Technology, Haifa, Israel]. In spite of the comparable formation rate constants obtained for A1D1 and collagen [1.81 +/- 0.25 compared with 3.71 +/- 0.26 mu mol of pentosidine (.) (mol of lysine)(-1) (.) year(-1) respectively], the higher pentosidine accumulation in collagen is consistent with its slower turnover (0.005 year(-1) compared with 0.134 year(-1) for A1D1). Pentosidine accumulation increased with decreasing buoyant density and decreasing turnover of the proteins from the most glycosaminoglycan-rich PG components (A1D1) to the least (A1D6), with respective k(F) values of 1.81 +/- 0.25 and 3.18 +/- 0.37 mu mol of pentosidine (.) (mol of lysine)(-1) (.) year(-1). We concluded that protein turnover is an important determinant of pentosidine accumulation in aggrecan and collagen of human IVD, as was found for articular cartilage. Correlation of pentosidine accumulation with protein half-life in both normal and degenerate discs further supports this finding.