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Brefeldin A promotes hydrolysis of sphingomyelin.

Publication ,  Journal Article
Linardic, CM; Jayadev, S; Hannun, YA
Published in: J Biol Chem
July 25, 1992

The hydrolysis of sphingomyelin (SM) is a key reaction in the "sphingomyelin cycle," which plays a role in the regulation of cell proliferation and differentiation (Okazaki, T., Bell, R. M., and Hannun, Y. A. (1989) J. Biol. Chem. 264, 19076-19080). SM is produced from endoplasmic reticulum-derived ceramide and is delivered to organelle membranes in a regulated manner, presumably through the same endomembrane trafficking system used for sorting and delivery of proteins. Since brefeldin A (BFA) interferes with this endomembrane trafficking system and thus alters normal membrane and organelle distribution, we investigated the effect of BFA on SM levels in HL-60 leukemia cells. BFA caused a dose-dependent decrease of 20-25% in cellular SM levels, with effects observed at concentrations of BFA as low as 0.10 microgram/ml. BFA effects on SM levels were noted as early as 5 min and were maximal by 20 min, with no further SM hydrolysis observed up to 60 min following treatment with BFA, suggesting the presence of a fixed SM-sensitive pool. BFA did not cause SM hydrolysis at 16 degrees C, a temperature that inhibits the effects of BFA on endomembrane mixing. The very early effects and temperature dependence of BFA-induced SM hydrolysis suggest that the mechanism of hydrolysis may be closely related to endomembrane mixing. These studies are beginning to define important interrelationships between membrane trafficking and topology, SM metabolism, and cell regulation.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

July 25, 1992

Volume

267

Issue

21

Start / End Page

14909 / 14911

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Temperature
  • Sphingomyelins
  • Kinetics
  • Hydrolysis
  • Cyclopentanes
  • Cell Division
  • Cell Differentiation
  • Brefeldin A
  • Biochemistry & Molecular Biology
 

Citation

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Linardic, C. M., Jayadev, S., & Hannun, Y. A. (1992). Brefeldin A promotes hydrolysis of sphingomyelin. J Biol Chem, 267(21), 14909–14911.
Linardic, C. M., S. Jayadev, and Y. A. Hannun. “Brefeldin A promotes hydrolysis of sphingomyelin.J Biol Chem 267, no. 21 (July 25, 1992): 14909–11.
Linardic CM, Jayadev S, Hannun YA. Brefeldin A promotes hydrolysis of sphingomyelin. J Biol Chem. 1992 Jul 25;267(21):14909–11.
Linardic, C. M., et al. “Brefeldin A promotes hydrolysis of sphingomyelin.J Biol Chem, vol. 267, no. 21, July 1992, pp. 14909–11.
Linardic CM, Jayadev S, Hannun YA. Brefeldin A promotes hydrolysis of sphingomyelin. J Biol Chem. 1992 Jul 25;267(21):14909–14911.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

July 25, 1992

Volume

267

Issue

21

Start / End Page

14909 / 14911

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Temperature
  • Sphingomyelins
  • Kinetics
  • Hydrolysis
  • Cyclopentanes
  • Cell Division
  • Cell Differentiation
  • Brefeldin A
  • Biochemistry & Molecular Biology