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Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2
Helsinki Eye Lab., Department of Ophthalmology, University of Helsinki, Helsinki, Finland; Public Health Genomic Unit, National Institute for Health and Welfare, Helsinki, Finland.
VTT Technical Research Centre of Finland, Espoo, Finland.
Public Health Genomic Unit, National Institute for Health and Welfare, Helsinki, Finland.
Helsinki Eye Lab., Department of Ophthalmology, University of Helsinki, Helsinki, Finland.
2012 (English)In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 53, no 11, p. 2286-2295Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2012. Vol. 53, no 11, p. 2286-2295
Keywords [en]
liquid chromatography-mass spectrometry; cornea; proinflammatory cytokines
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-65692DOI: 10.1194/jlr.M026732ISI: 000309672100005PubMedID: 22899568Scopus ID: 2-s2.0-84867363418OAI: oai:DiVA.org:oru-65692DiVA, id: diva2:1189762
Note

Funding Agencies:

Sigrid Juselius Foundation  

Finnish Academy  132 629  128 128 

Helsinki University Central Hospital Research Foundation  

Finnish Eye Foundation 

Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2018-03-13Bibliographically approved

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Hyötyläinen, Tuulia

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