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Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2
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- Robciuc, A. (author)
- Helsinki Eye Lab., Department of Ophthalmology, University of Helsinki, Helsinki, Finland; Public Health Genomic Unit, National Institute for Health and Welfare, Helsinki, Finland
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- Hyötyläinen, Tuulia, 1971- (author)
- VTT Technical Research Centre of Finland, Espoo, Finland
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- Jauhiainen, M. (author)
- Public Health Genomic Unit, National Institute for Health and Welfare, 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, Finland VTT Technical Research Centre of Finland, Espoo, Finland (creator_code:org_t)
- American Society for Biochemistry and Molecular Biology, 2012
- 2012
- English.
- In: Journal of Lipid Research. - : American Society for Biochemistry and Molecular Biology. - 0022-2275 .- 1539-7262. ; 53:11, s. 2286-2295
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- liquid chromatography-mass spectrometry; cornea; proinflammatory cytokines
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- ref (subject category)
- art (subject category)
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