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dc.contributor.authorValvatne, Monica Dalva
dc.contributor.authorel Jellas, Khadija
dc.contributor.authorGravdal, Anny
dc.contributor.authorNjølstad, Pål Rasmus
dc.contributor.authorMolven, Anders
dc.contributor.authorFjeld, Karianne
dc.contributor.authorLugea, Aurelia
dc.contributor.authorPandol, Stephen J
dc.contributor.authorWaldron, Richard T
dc.contributor.authorLavik, Ida
dc.contributor.authorJohansson, Bente B.
dc.date.accessioned2021-07-01T09:11:07Z
dc.date.available2021-07-01T09:11:07Z
dc.date.created2020-01-22T09:26:53Z
dc.date.issued2020
dc.identifier.issn2073-4409
dc.identifier.urihttps://hdl.handle.net/11250/2762731
dc.description.abstractMutations 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.isoengen_US
dc.publisherMDPIen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titlePathogenic Carboxyl Ester Lipase (CEL) Variants Interact with the Normal CEL Protein in Pancreatic Cellsen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2020 The Authorsen_US
dc.source.articlenumber244en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.3390/cells9010244
dc.identifier.cristin1779695
dc.source.journalCellsen_US
dc.identifier.citationCells. 2020, 9(1), 244en_US
dc.source.volume9en_US
dc.source.issue1en_US


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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal