ArticleMolecular pathology : MP1998
Intracellular accumulation of the amyloidogenic L68Q variant of human cystatin C in NIH/3T3 cells.
Article in Molecular pathology : MP, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 32 citations in OpenAlex.
- Basement membrane remodeling with fibroblast activation and cystatin C aggregation in cerebral vessels of hereditary cystatin C amyloid angiopathy.Acta neuropathologica communications · 2026Article
- Investigating APOE, APP-Aβ metabolism genes and Alzheimer's disease GWAS hits in brain small vessel ischemic disease.Scientific reports · 2020Article
- Pathological changes in basement membranes and dermal connective tissue of skin from patients with hereditary cystatin C amyloid angiopathy.Laboratory investigation; a journal of technical methods and pathology · 2017Article
- Evidence of Alternative Cystatin C Signal Sequence Cleavage Which Is Influenced by the A25T Polymorphism.PloS one · 2016Article
- The role of cystatin C in cerebral amyloid angiopathy and stroke: cell biology and animal models.Brain pathology (Zurich, Switzerland) · 2006Review
- Cystatin C uptake in the eye.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2005Article
- Cathepsin B in the rat eye.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2003Article
- Lysosomal enzymes, cathepsins in brain tumour invasion.Journal of neuro-oncology · 2002Review
- Cystatin C--properties and use as diagnostic marker.Advances in clinical chemistry · 2000Review
- Cystatin C is a disease-associated protein subject to multiple regulation.Immunology and cell biologyReview
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
aimTo study the cellular transport of L68Q cystatin C, the cystatin variant causing amyloidosis and brain haemorrhage in patients suffering from hereditary cystatin C amyloid angiopathy (HCCAA).
methodsExpression vectors for wild-type and L68Q cystatin C were constructed and used to transfect mouse NIH/3T3 cells. Stable cell clones were isolated after cotransfection with pSV2neo. Clones expressing human wild-type and L68Q cystatin C were compared with respect to secreted cystatin C by enzyme linked immunosorbent assay (ELISA), and for intracellular cystatin C by western blotting and immunofluorescence cytochemistry. Colocalisation studies in cells were performed by double staining with antibodies against human cystatin C and marker proteins for lysosomes, the Golgi apparatus, or the endoplasmic reticulum, and evaluated by confocal microscopy.
resultsConcentrations of human cystatin C secreted from transfected NIH/3T3 cells were similar to those secreted from human cells in culture. In general, clones expressing the gene encoding L68Q cystatin C secreted slightly lower amounts of the protein than clones expressing wild-type human cystatin C. Both immunofluorescence cytochemistry and western blotting experiments showed an increased accumulation of cystatin C in cells expressing the gene encoding L68Q cystatin C compared with cells expressing the gene for the wild-type protein. The intracellularly accumulating L68Q cystatin C was insoluble and located mainly in the endoplasmic reticulum.
conclusionsThe cellular transport of human cystatin C is impeded by the pathogenic amino acid substitution Leu68-->Gln. The resulting intracellular accumulation and increased localised concentration of L68Q cystatin C might be an important event in the molecular pathophysiology of amyloid formation and brain haemorrhage in patients with HCCAA.
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