Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0376606 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1539-7262 (Electronic) Linking ISSN: 00222275 NLM ISO Abbreviation: J Lipid Res Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York] : Elsevier
      Original Publication: Memphis, Lipid Research, inc.
    • Subject Terms:
    • Abstract:
      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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    • Accession Number:
      0 (Interleukin-8)
      0 (Sphingomyelins)
      EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
    • Publication Date:
      Date Created: 20120818 Date Completed: 20130306 Latest Revision: 20211021
    • Publication Date:
      20221213
    • Accession Number:
      PMC3465998
    • Accession Number:
      10.1194/jlr.M026732
    • Accession Number:
      22899568