Pathogenic Carboxyl Ester Lipase (CEL) Variants Interact with the Normal CEL Protein in Pancreatic Cells
dc.contributor.author | Valvatne, Monica Dalva | |
dc.contributor.author | el Jellas, Khadija | |
dc.contributor.author | Gravdal, Anny | |
dc.contributor.author | Njølstad, Pål Rasmus | |
dc.contributor.author | Molven, Anders | |
dc.contributor.author | Fjeld, Karianne | |
dc.contributor.author | Lugea, Aurelia | |
dc.contributor.author | Pandol, Stephen J | |
dc.contributor.author | Waldron, Richard T | |
dc.contributor.author | Lavik, Ida | |
dc.contributor.author | Johansson, Bente B. | |
dc.date.accessioned | 2021-07-01T09:11:07Z | |
dc.date.available | 2021-07-01T09:11:07Z | |
dc.date.created | 2020-01-22T09:26:53Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 2073-4409 | |
dc.identifier.uri | https://hdl.handle.net/11250/2762731 | |
dc.description.abstract | Mutations in the gene encoding the digestive enzyme carboxyl ester lipase (CEL) are linked to pancreatic disease. The CEL variant denoted CEL-HYB predisposes to chronic pancreatitis, whereas the CEL-MODY variant causes MODY8, an inherited disorder of endocrine and exocrine pancreatic dysfunction. Both pathogenic variants exhibit altered biochemical and cellular properties compared with the normal CEL protein (CEL-WT, wild type). We here aimed to investigate effects of CEL variants on pancreatic acinar and ductal cell lines. Following extracellular exposure, CEL-HYB, CEL-MODY, and CEL-WT were endocytosed. The two pathogenic CEL proteins significantly reduced cell viability compared with CEL-WT. We also found evidence of CEL uptake in primary human pancreatic acinar cells and in native ductal tissue. Moreover, coexpression of CEL-HYB or CEL-MODY with CEL-WT affected secretion of the latter, as CEL-WT was observed to accumulate intracellularly to a higher degree in the presence of either pathogenic variant. Notably, in coendocytosis experiments, both pathogenic variants displayed a modest effect on cell viability when CEL-WT was present, indicating that the normal protein might diminish toxic effects conferred by CEL-HYB and CEL-MODY. Taken together, our findings provide valuable insight into how the pathogenic CEL variants predispose to pancreatic disease and why these disorders develop slowly over time. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | MDPI | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Pathogenic Carboxyl Ester Lipase (CEL) Variants Interact with the Normal CEL Protein in Pancreatic Cells | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2020 The Authors | en_US |
dc.source.articlenumber | 244 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.3390/cells9010244 | |
dc.identifier.cristin | 1779695 | |
dc.source.journal | Cells | en_US |
dc.identifier.citation | Cells. 2020, 9(1), 244 | en_US |
dc.source.volume | 9 | en_US |
dc.source.issue | 1 | en_US |
Tilhørende fil(er)
Denne innførselen finnes i følgende samling(er)
-
Department of Clinical Medicine [2034]
-
Registrations from Cristin [9450]