onr:"swepub:oai:lup.lub.lu.se:176e3a5d-c9d8-4de8-b65c-d5cc2dd07f49"
Sökning: onr:"swepub:oai:lup.lub.lu.se:176e3a5d-c9d8-4de8-b65c-d5cc2dd07f49" > Intracellular accum...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 03691naa a2200349 4500 | |
| 001 | oai:lup.lub.lu.se:176e3a5d-c9d8-4de8-b65c-d5cc2dd07f49 | |
| 003 | SwePub | |
| 008 | 160401s1998 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://lup.lub.lu.se/record/11139102 URI |
| 040 | a (SwePub)lu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a art2 swepub-publicationtype |
| 072 | 7 | a ref2 swepub-contenttype |
| 100 | 1 | a Bjarnadottir, M4 aut |
| 245 | 1 0 | a Intracellular accumulation of the amyloidogenic L68Q variant of cystatin C in NIH/3T3 cells |
| 264 | 1 | c 1998 |
| 520 | a AIM: To 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). METHODS: Expression 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. RESULTS: Concentrations 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. CONCLUSIONS: The 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. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmakologi och toxikologi0 (SwePub)301022 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmacology and Toxicology0 (SwePub)301022 hsv//eng |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Läkemedelskemi0 (SwePub)301032 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medicinal Chemistry0 (SwePub)301032 hsv//eng |
| 700 | 1 | a Wulff, B4 aut |
| 700 | 1 | a Keppler, D4 aut |
| 700 | 1 | a Moin, K4 aut |
| 700 | 1 | a Sloane, B4 aut |
| 700 | 1 | a Grubb, A4 aut |
| 700 | 1 | a Abrahamson, Magnusu Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine4 aut0 (Swepub:lu)kkem-mab |
| 710 | 2 | a Avdelningen för klinisk kemi och farmakologib Institutionen för laboratoriemedicin4 org |
| 773 | 0 | t Molecular Pathologyg 51:6, s. 317-326q 51:6<317-326x 1366-8714 |
| 856 | 4 | u http://mp.bmj.com/cgi/reprint/51/6/317x freey FULLTEXT |
| 856 | 4 8 | u https://lup.lub.lu.se/record/1113910 |
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