Hereditary cystatin C amyloid angiopathy: monitoring the presence of the Leu-68-->Gln cystatin C variant in cerebrospinal fluids and monocyte cultures by MS
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Asgeirsson, BHaebel, S
Thorsteinsson, L
Helgason, E
Gudmundsson, K O
Gudmundsson, G
Roepstorff, P
Issue Date
1998-02-01
Metadata
Show full item recordCitation
Hereditary cystatin C amyloid angiopathy: monitoring the presence of the Leu-68-->Gln cystatin C variant in cerebrospinal fluids and monocyte cultures by MS. 1998, 329 ( Pt 3):497-503 Biochem. J.Abstract
Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant condition in which the patients suffer at an early age from repeated cerebral haemorrhages. The development of HCCAA is directly linked to a Leu-68-->Gln (L68Q) mutation in the cystatin C protein sequence. The concentration of cystatin C in cerebrospinal fluid (CSF) of HCCAA patients is markedly diminished and cultivated monocytes from affected individuals accumulate cystatin C. The goal of this work was to characterize cystatin C isolated from CSF and monocyte cultures originating from healthy persons and HCCAA patients with respect to the L68Q mutation. Cystatin C was isolated by carboxymethylpapain affinity chromatography. Proteins from CSF and monocyte cultures that bound specifically to the carboxymethylated papain column were resolved by reverse-phase HPLC chromatography and tryptic peptides were subsequently analysed by matrix-assisted laser desorption ionization MS. No evidence for mutated cystatin C protein was found in CSF samples from healthy subjects or HCCAA patients, but approx. 60% of the protein was found to be hydroxylated on Pro-3. No evidence was found for secretion of mutated cystatin C from HCCAA monocytes. However, we obtained evidence for the presence of mutated cystatin C in HCCAA monocytes. These results support the conclusion that the mutated cystatin C is retained in association with the monocytes and not secreted. An increased intracellular concentration would presumably promote the aggregation and denaturation of the mutated cystatin C, leading to the formation of amyloid fibrils and cell death.Description
To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldAdditional Links
http://www.biochemj.org/bj/329/0497/3290497.pdfCollections
Related articles
- The cerebral hemorrhage-producing cystatin C variant (L68Q) in extracellular fluids.
- Authors: Bjarnadottir M, Nilsson C, Lindström V, Westman A, Davidsson P, Thormodsson F, Blöndal H, Gudmundsson G, Grubb A
- Issue date: 2001 Mar
- On the role of monocytes/macrophages in the pathogenesis of central nervous system lesions in hereditary cystatin C amyloid angiopathy.
- Authors: Thorsteinsson L, Georgsson G, Asgeirsson B, Bjarnadóttir M, Olafsson I, Jensson O, Gudmundsson G
- Issue date: 1992 Apr
- The amino terminal portion of cerebrospinal fluid cystatin C in hereditary cystatin C amyloid angiopathy is not truncated: direct sequence analysis from agarose gel electropherograms.
- Authors: Olafsson I, Gudmundsson G, Abrahamson M, Jensson O, Grubb A
- Issue date: 1990 Feb
- Two stable unfolding intermediates of the disease-causing L68Q variant of human cystatin C.
- Authors: Gerhartz B, Ekiel I, Abrahamson M
- Issue date: 1998 Dec 8
- No mutations in cystatin C gene in cerebral amyloid angiopathy with cystatin C deposition.
- Authors: Nagai A, Kobayashi S, Shimode K, Imaoka K, Umegae N, Fujihara S, Nakamura M
- Issue date: 1998 Jan