The cerebral hemorrhage-producing cystatin C variant (L68Q) in extracellular fluids
| Autor: | Pia Davidsson, Hannes Blöndal, Finnbogi R. Thormodsson, Gunnar Gudmundsson, Maria Bjarnadottir, Veronica Lindström, Carol L. Nilsson, Anders Grubb, Ann Westman |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Amyloid Population Enzyme-Linked Immunosorbent Assay urologic and male genital diseases Reference Values Internal Medicine medicine Extracellular Humans Cystatin C education reproductive and urinary physiology Cerebral Hemorrhage education.field_of_study biology Chemistry Genetic Carrier Screening Amyloidosis Genetic Variation Cerebrospinal Fluid Proteins Middle Aged Hereditary cystatin C amyloid angiopathy medicine.disease Cystatins Cysteine protease female genital diseases and pregnancy complications Cerebral Amyloid Angiopathy Amino Acid Substitution Biochemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization biology.protein Cystatin Extracellular Space |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1744-2818 1350-6129 |
| DOI: | 10.3109/13506120108993809 |
| Popis: | 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, but 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 precipitating aggregates. |
| Databáze: | OpenAIRE |
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