Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
26
|
pubmed:dateCreated |
1990-10-11
|
pubmed:abstractText |
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.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcitriol,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylcholines,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingomyelins
|
pubmed:status |
MEDLINE
|
pubmed:month |
Sep
|
pubmed:issn |
0021-9258
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
265
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
15823-31
|
pubmed:dateRevised |
2007-11-14
|
pubmed:meshHeading |
pubmed-meshheading:2394750-Calcitriol,
pubmed-meshheading:2394750-Cell Differentiation,
pubmed-meshheading:2394750-Cell Division,
pubmed-meshheading:2394750-Cell Line,
pubmed-meshheading:2394750-Ceramides,
pubmed-meshheading:2394750-Humans,
pubmed-meshheading:2394750-Kinetics,
pubmed-meshheading:2394750-Leukemia, Promyelocytic, Acute,
pubmed-meshheading:2394750-Phosphatidylcholines,
pubmed-meshheading:2394750-Phospholipids,
pubmed-meshheading:2394750-Sphingomyelins
|
pubmed:year |
1990
|
pubmed:articleTitle |
Role of ceramide as a lipid mediator of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation.
|
pubmed:affiliation |
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|