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

Alexandra Robciuc, Tuulia Hyötyläinen, Matti Jauhiainen, Juha M. Holopainen (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

12 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2286-2295
JournalJournal of Lipid Research
Volume53
Issue number11
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

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Sphingomyelin Phosphodiesterase
Ceramides
Triglycerides
Cytokines
Lipids
Diacylglycerol O-Acyltransferase
Sphingomyelins
Interleukin-8
Osmolar Concentration
Enzyme activity
Hydrolysis
Transcription
Epithelial Cells
Sodium
Membranes
Enzymes
Tissue
Lipid Droplets

Cite this

Robciuc, Alexandra ; Hyötyläinen, Tuulia ; Jauhiainen, Matti ; Holopainen, Juha M. / Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2. In: Journal of Lipid Research. 2012 ; Vol. 53, No. 11. pp. 2286-2295.
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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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Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2. / Robciuc, Alexandra; Hyötyläinen, Tuulia; Jauhiainen, Matti; Holopainen, Juha M. (Corresponding Author).

In: Journal of Lipid Research, Vol. 53, No. 11, 2012, p. 2286-2295.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2

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AB - 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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