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Role of ceramide as a lipid mediator of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation.
Open accessAbstract
The treatment of HL-60 myelocytic leukemia cells with 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) resulted in the activation of a neutral sphingomyelinase and in sphingomyelin turnover (Okazaki, T., Bell, R., and Hannun, Y. (1989) J. Biol. Chem. 264, 19076-19080). In this paper, the effects of 1,25-(OH)2D3 on the product of sphingomyelin hydrolysis, ceramide, and the possible function of ceramide as a lipid mediator of the effects of 1,25-(OH)2D3 on HL-60 cell differentiation were investigated. Treatment of HL-60 cells with 1,25-(OH)2D3 resulted in a time- and dose-dependent increase in ceramide mass levels. Ceramide levels peaked at 2 h following treatment of HL-60 cells with 100 nM 1,25-(OH)2D3 with an increase of 41% over base line. The mass of generated ceramide (13 +/- 2 pmol/nmol of phospholipid) agreed with the mass of hydrolyzed sphingomyelin (17 +/- 4 pmol/nmol of phospholipid). Cell-permeable ceramides with shorter N-acyl chains induced HL-60 cell differentiation at subthreshold concentrations of 1,25-(OH)2D3. Higher concentrations of cell-permeable ceramides potently induced HL-60 cell differentiation independent of 1,25-(OH)2D3. A 2-h exposure of HL-60 cells to N-acetyl-sphingosine was sufficient to cause differentiation. Morphologically, N-acetylsphingosine caused a similar monocytic differentiation of HL-60 cells as did 1,25-(OH)2D3. Exogenous ceramide was further metabolized to sphingomyelin and other sphingolipids, but no conversion to sphingosine was detected. Moreover, sphingosine and its analogs failed to affect monocytic differentiation of HL-60 cells in response to subthreshold 1,25-(OH)2D3, indicating that the effect of ceramide was independent of sphingosine generation. These studies demonstrate that ceramide is a lipid mediator that may transduce the action of 1,25-(OH)2D3 on HL-60 cell differentiation.
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Cites
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751
Cited by
Programmed Cell Death Induced by Ceramide
Obeid, L. M., Linardic, C. M., Karolak, L. A., & Hannun, Y. A. (1993) · Science · doi:10.1126/science.8456305 · Cited by 1,794
Self-citationFatty acid-induced β cell apoptosis: A link between obesity and diabetes
Shimabukuro, M., Zhou, Y.-T., Levi, M., & Unger, R. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2498 · Cited by 1,142
Long Chain Ceramides Activate Protein Phosphatase-1 and Protein Phosphatase-2A
Chalfant, C. E., Kishikawa, K., Mumby, M. C., Kamibayashi, C., Bielawska, A., & Hannun, Y. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.29.20313 · Cited by 300
Self-citationRole of ceramide-activated protein phosphatase in ceramide-mediated signal transduction.
Wolff, R. A., Dobrowsky, R. T., Bielawska, A., Obeid, L. M., & Hannun, Y. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32212-3 · Cited by 285
Self-citationBallou, L. R., Chao, C. P., Holness, M. A., Barker, S. C., & Raghow, R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)88663-5 · Cited by 272
Metadata
- Authors
- Okazaki, T., Bielawska, A., Bell, R. M., & Hannun, Y. A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1990-09
- Volume
- 265
- Issue
- 26
- Pages
- 15823-15831
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1542941723
- Cited by
- 471
- References
- 1
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Okazaki, T., Bielawska, A., Bell, R. M., & Hannun, Y. A. (1990). Role of ceramide as a lipid mediator of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation. Journal of Biological Chemistry. https://doi.org/10.1016/s0021-9258(18)55472-7
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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