The cerebral hemorrhage-producing cystatin C variant (L68Q) in extracellular fluids

被引:37
作者
Bjarnadottir, M
Nilsson, C
Lindström, V
Westman, A
Davidsson, P
Thormodsson, F
Blöndal, H
Gudmundsson, G
Grubb, A [1 ]
机构
[1] Univ Lund Hosp, Dept Clin Chem, Inst Lab Med, S-22185 Lund, Sweden
[2] Univ Gothenburg, Dept Biochem Med, Gothenburg, Sweden
[3] Univ Goteburg, Expt Neurosci Sect, Dept Clin Neurosci, Sahlgrens Univ Hosp, Molndal, Sweden
[4] Univ Iceland, Fac Med, Dept Anat, Reykjavik, Iceland
[5] Natl Univ Hosp, Dept Neurol, Reykjavik, Iceland
来源
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS | 2001年 / 8卷 / 01期
关键词
amyloidosis; cerebral hemorrhage; cystatin C; HCCAA; MALDI-TOFMS; mass spectrometry;
D O I
10.3109/13506120108993809
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A variant of the normal extracellular cysteine protease inhibitor cystatin C (L68Q-cystatin C), is the amyloid precursor in hereditary cystatin C amyloid angiopathy (HCCAA). It has been suggested that the mutation causes cellular entrapment of L68Q-cystatin C in vivo and that the variant protein is not secreted to extracellular fluids. In order to test this hypothesis, we used matrix-assisted laser desorption ionization time-of-flight mass spectrometry in an effort to demonstrate the presence of L68Q- along with wildtype cystatin C in plasma and cerebrospinal fluid (CSF) of HCCAA-patients. Plasma from all five investigated HCCAA-patients contained both L68Q- and wildtype cystatin C. The presence of approximately equal amounts of cystatin C dimers and monomers was demonstrated in plasma from HCCAA-patients, whereas only monomers could be found in normal plasma. L68Q-wildtype-cystatin C heterodimers seem to be present in the dimeric cystatin C population. CSF from six HCCAA-patients also contained cystatin C-dimers and monomers, bur the dimeric fraction was minute. CSF from control patients did not contain dimeric cystatin C. These results suggest that the milieu of L68Q-cystatin C is important for its stability and dimerization status and that certain milieus might hinder its further development into oligomers, amyloid fibrils and other precipiting aggregates.
引用
收藏
页码:1 / 10
页数:10
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