β2-微球蛋白淀粉样变的分子异质性及晚期糖基化终产物修饰

Molecular heterogeneity of amyloid beta2-microglobulin and modification with advanced glycation end products.

作者信息

Mironova R, Niwa T

机构信息

Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia.

出版信息

J Chromatogr B Biomed Sci Appl. 2001 Jul 5;758(1):109-15. doi: 10.1016/s0378-4347(01)00139-6.

DOI:10.1016/s0378-4347(01)00139-6

PMID:11482729

Abstract

By using liquid chromatography-electrospray ionization mass spectrometry, Western blotting and N-terminal amino acid sequence analysis, we characterized the molecular heterogeneity and advanced glycation end product (AGE) modification of beta2-microglobulin (beta2m) extracted from the amyloid tissue of a hemodialysis patient. Amyloid beta2m was composed of full-length beta2m, truncated beta2m and dimer beta2m. Truncated beta2m and dimer beta2m were modified with AGEs such as imidazolone and N(e)-(carboxymethyl)lysine, and showed fluorescence characteristic of AGE. Truncated beta2m species were formed by cleavage between amino acid residues of Pro6/Ile7, Gln/Val9 and Val9/Tyr10. Heterogeneous dimer beta2m species showed the molecular masses of 22,591 and 22 675, which resulted from cross-linking between truncated beta2m.

摘要

通过使用液相色谱-电喷雾电离质谱法、蛋白质免疫印迹法和N端氨基酸序列分析，我们对从一名血液透析患者的淀粉样组织中提取的β2-微球蛋白（β2m）的分子异质性和晚期糖基化终产物（AGE）修饰进行了表征。淀粉样β2m由全长β2m、截短的β2m和二聚体β2m组成。截短的β2m和二聚体β2m被咪唑啉酮和Nε-（羧甲基）赖氨酸等AGE修饰，并表现出AGE的荧光特性。截短的β2m物种是由Pro6/Ile7、Gln/Val9和Val9/Tyr10氨基酸残基之间的裂解形成的。异质二聚体β2m物种的分子量分别为22,591和22,675，这是由截短的β2m之间的交联产生的。