Journal
JOURNAL OF LIPID RESEARCH
Volume 53, Issue 11, Pages 2286-2295Publisher
ELSEVIER
DOI: 10.1194/jlr.M026732
Keywords
liquid chromatography-mass spectrometry; cornea; proinflammatory cytokines
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Funding
- 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.-Robciuc, A., T. Hyotylainen, M. Jauhiainen, and J. M. Holopainen. Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2. J. Lipid Res. 2012. 53: 2286-2295.
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