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Ceramide: a new lipid "second messenger"?

A H Merrill1

  • 1Rollins Research Center, Emory University School of Medicine, Atlanta, GA 30322.

Nutrition Reviews
|March 1, 1992
PubMed
Summary
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1-Alpha, 25-dihydroxyvitamin D3 and other factors induce sphingomyelin turnover to ceramide in HL-60 cells. This lipid signaling pathway mediates cell growth and differentiation, highlighting the role of sphingolipids.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Sphingolipids, such as ceramide, are critical signaling molecules involved in cellular processes.
  • The biologically active form of vitamin D (1-Alpha, 25-dihydroxyvitamin D3) plays a role in cell regulation.
  • Tumor necrosis factor alpha and gamma-interferon are cytokines with diverse cellular functions.

Purpose of the Study:

  • To investigate the role of 1-Alpha, 25-dihydroxyvitamin D3, tumor necrosis factor alpha, and gamma-interferon in sphingomyelin metabolism.
  • To determine if ceramide formation mediates cell growth and differentiation induced by these factors.
  • To explore the involvement of lipid second messenger pathways in the action of vitamin D and related factors.

Main Methods:

  • Treatment of HL-60 cells with 1-Alpha, 25-dihydroxyvitamin D3, tumor necrosis factor alpha, and gamma-interferon.

Related Experiment Videos

  • Measurement of sphingomyelin turnover and ceramide formation.
  • Assessment of cell growth and differentiation.
  • Addition of exogenous ceramides to evaluate their effect on differentiation.

    • Main Results:

    • 1-Alpha, 25-dihydroxyvitamin D3, tumor necrosis factor alpha, and gamma-interferon induce sphingomyelin turnover to ceramide in HL-60 cells.
    • The timing of ceramide formation correlates with the induction of cell growth and differentiation.
    • Exogenous ceramides alone can induce differentiation in HL-60 cells.

    Conclusions:

    • The action of 1-Alpha, 25-dihydroxyvitamin D3 and other nutritionally relevant factors may be mediated by lipid second messenger pathways involving sphingolipids.
    • Ceramide formation is a key mediator in the growth and differentiation processes induced by these signaling molecules.
    • This study elucidates a novel mechanism for vitamin D and cytokine action through sphingolipid metabolism.