PDF(Pubmed)
Abstract：
UNASSIGNED: Protein post-translational modifications (PTMs) have been associated with aging and age-related diseases. PTMs are particularly impactful in long-lived proteins, such as those found in the ocular lens, because they accumulate with age. Two PTMs that lead to protein-protein crosslinks in aged and cataractous lenses are dehydroalanine (DHA) and dehydrobutyrine (DHB); formed from cysteine/serine and threonine residues, respectively. The purpose of this study was to quantitate DHA and DHB in human lens proteins as a function of age and cataract status.
UNASSIGNED: Human lenses of various ages were divided into five donor groups: transparent lenses (18-22-year-old, 48-64-year-old, and 70-93-year-old) and cataractous human lenses of two age groups (48-64-year-old lenses, and 70-93-year-old lenses) and were subjected to proteomic analysis. Relative DHA and DHB peptide levels were quantified and compared to their non-modified peptide counterparts.
UNASSIGNED: For most lens proteins containing DHA or DHB, higher amounts of DHA- and DHB-modified peptides were detected in aged and cataractous lenses. DHA-containing peptides were classified into three groups based on abundance changes with age and cataract: those that (1) increased only in age-related nuclear cataract (ARNC), (2) increased in aged and cataractous lenses, and (3) decreased in aged lenses and ARNC. There was no indication that DHA or DHB levels were dependent on lens region. In most donor groups, proteins with DHA and DHB were more likely to be found among urea-insoluble proteins rather than among water- or urea-soluble proteins.
UNASSIGNED: DHA and DHB formation may induce structural effects that make proteins less soluble in water that leads to age-related protein insolubility and possibly aggregation and light scattering.
UNASSIGNED: Human lenses of various ages were divided into five donor groups: transparent lenses (18-22-year-old, 48-64-year-old, and 70-93-year-old) and cataractous human lenses of two age groups (48-64-year-old lenses, and 70-93-year-old lenses) and were subjected to proteomic analysis. Relative DHA and DHB peptide levels were quantified and compared to their non-modified peptide counterparts.
UNASSIGNED: For most lens proteins containing DHA or DHB, higher amounts of DHA- and DHB-modified peptides were detected in aged and cataractous lenses. DHA-containing peptides were classified into three groups based on abundance changes with age and cataract: those that (1) increased only in age-related nuclear cataract (ARNC), (2) increased in aged and cataractous lenses, and (3) decreased in aged lenses and ARNC. There was no indication that DHA or DHB levels were dependent on lens region. In most donor groups, proteins with DHA and DHB were more likely to be found among urea-insoluble proteins rather than among water- or urea-soluble proteins.
UNASSIGNED: DHA and DHB formation may induce structural effects that make proteins less soluble in water that leads to age-related protein insolubility and possibly aggregation and light scattering.
摘要：
■蛋白质翻译后修饰（PTM）与衰老和与年龄有关的疾病有关。PTM在长寿命蛋白质中特别有影响力，比如在目镜中发现的，因为它们随着年龄的增长而积累。在老年和白内障晶状体中导致蛋白质-蛋白质交联的两种PTM是脱氢丙氨酸（DHA）和脱氢丁酸（DHB）；由半胱氨酸/丝氨酸和苏氨酸残基形成，分别。这项研究的目的是定量人晶状体蛋白中的DHA和DHB与年龄和白内障状态的关系。
■将不同年龄的人类镜片分为五个供体组：透明镜片（18-22岁，48-64岁,和70-93岁）和两个年龄组的白内障人类晶状体（48-64岁的晶状体，和70-93岁的镜片），并进行了蛋白质组学分析。定量相对DHA和DHB肽水平并与其未修饰的肽对应物进行比较。
■对于大多数含有DHA或DHB的晶状体蛋白，在老年和白内障晶状体中检测到较高量的DHA和DHB修饰肽。根据年龄和白内障的丰度变化，将含DHA的肽分为三组：（1）仅在年龄相关性核性白内障（ARNC）中增加，(2)老年和白内障晶状体增加，(3)老年晶状体和ARNC下降。没有迹象表明DHA或DHB水平依赖于晶状体区域。在大多数捐赠团体中，含有DHA和DHB的蛋白质更可能存在于尿素不溶性蛋白质中,而不是水溶性或尿素可溶性蛋白质中.
■DHA和DHB的形成可能会引起结构效应，使蛋白质在水中的溶解度降低，从而导致与年龄相关的蛋白质不溶性以及可能的聚集和光散射。
■将不同年龄的人类镜片分为五个供体组：透明镜片（18-22岁，48-64岁,和70-93岁）和两个年龄组的白内障人类晶状体（48-64岁的晶状体，和70-93岁的镜片），并进行了蛋白质组学分析。定量相对DHA和DHB肽水平并与其未修饰的肽对应物进行比较。
■对于大多数含有DHA或DHB的晶状体蛋白，在老年和白内障晶状体中检测到较高量的DHA和DHB修饰肽。根据年龄和白内障的丰度变化，将含DHA的肽分为三组：（1）仅在年龄相关性核性白内障（ARNC）中增加，(2)老年和白内障晶状体增加，(3)老年晶状体和ARNC下降。没有迹象表明DHA或DHB水平依赖于晶状体区域。在大多数捐赠团体中，含有DHA和DHB的蛋白质更可能存在于尿素不溶性蛋白质中,而不是水溶性或尿素可溶性蛋白质中.
■DHA和DHB的形成可能会引起结构效应，使蛋白质在水中的溶解度降低，从而导致与年龄相关的蛋白质不溶性以及可能的聚集和光散射。
