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Hyperosmolarity-ind...
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Robciuc, A.Helsinki Eye Lab., Department of Ophthalmology, University of Helsinki, Helsinki, Finland; Public Health Genomic Unit, National Institute for Health and Welfare, Helsinki, Finland
(author)
Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2
- Article/chapterEnglish2012
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American Society for Biochemistry and Molecular Biology,2012
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LIBRIS-ID:oai:DiVA.org:oru-65692
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-65692URI
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https://doi.org/10.1194/jlr.M026732DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Funding Agencies:Sigrid Juselius Foundation Finnish Academy 132 629 128 128 Helsinki University Central Hospital Research Foundation Finnish Eye Foundation
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Hyperosmolarity (HO) imposes a remarkable stress on membranes, especially in tissues in direct contact with the external environment. Our efforts were focused on revealing stress-induced lipid changes that precede the inflammatory cytokine response in human corneal epithelial cells exposed to increasing osmolarity. We used a lipidomic analysis that detected significant and systematic changes in the lipid profile, highly correlated with sodium concentrations in the medium. Ceramides and triglycerides (TGs) were the most-responsive lipid classes, with gradual increases of up to 2- and 3-fold, respectively, when compared with control. The source of ceramide proved to be sphingomyelin hydrolysis, and neutral sphingomyelinase 2 (NSM2) activity showed a 2-fold increase 1 h after HO stress, whereas transcription increased 3-fold. Both TG accumulation and IL-8 secretion were shown to be dependent on ceramide production by specific knock-down of NSM2. In HCE cells, diglyceride acyltransferase 1 was responsible for the TG synthesis, but the enzyme activity had no effect on cytokine secretion. Hence, NSM2 plays a key role in the cellular response to hyperosmolar stress, and its activity regulates both cytokine secretion and lipid droplet formation.
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Hyötyläinen, Tuulia,1971-VTT Technical Research Centre of Finland, Espoo, Finland(Swepub:oru)tihn
(author)
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Jauhiainen, M.Public Health Genomic Unit, National Institute for Health and Welfare, Helsinki, Finland
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Holopainen, J. M.Helsinki Eye Lab., Department of Ophthalmology, University of Helsinki, Helsinki, Finland
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Helsinki Eye Lab., Department of Ophthalmology, University of Helsinki, Helsinki, Finland; Public Health Genomic Unit, National Institute for Health and Welfare, Helsinki, FinlandVTT Technical Research Centre of Finland, Espoo, Finland
(creator_code:org_t)
Related titles
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In:Journal of Lipid Research: American Society for Biochemistry and Molecular Biology53:11, s. 2286-22950022-22751539-7262
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