Document Detail


Changes in the levels of inositol lipids and phosphates during the differentiation of HL60 promyelocytic cells towards neutrophils or monocytes.
MedLine Citation:
PMID:  1684044     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HL60 cells were adapted to grow in a serum-free medium containing 1 mg l-1 inositol, in which they differentiated normally towards neutrophils (in 0.9% by volume dimethylsulphoxide) and towards monocytes (in 10 nM phorbol myristate acetate). Cells that had been equilibrium-labelled with [2-3H]myo-inositol contained a complex pattern of inositol metabolites, several of which were at relatively high concentrations. These included InsP5 and InsP6, which were present at concentrations of about 25 microM and 60 microM, respectively. Striking and different changes occurred in the levels of some of the inositol polyphosphates as the cells differentiated towards either neutrophils or monocytes. Most notable were a large but gradual accumulation of Ins(1,3,4,5,6)P5 as HL60 cells decreased in size and acquired neutrophil characteristics, and much more rapid and sequential declines in InsP4, InsP5 and InsP6 as the cells started to take on monocyte character. There was a marked accumulation of free inositol and of phosphatidylinositol in the cells during neutrophil differentiation, probably caused at least in part by an increased rate of inositol uptake providing an increased intracellular inositol supply. The same accumulation of Ins(1,3,4,5,6)P5 occurred during neutrophil differentiation, whether it was induced by dimethylsulphoxide or by a combination of retinoic acid and a T-lymphocyte cell line-derived differentiation factor. Ins(1,4,5)P3, a physiological intracellular mediator of Ca2+ release from membrane stores, did not change in concentration during these differentiation processes. These observations suggest that some of the more abundant cellular inositol polyphosphates play some important, but not yet understood, role either in the processes of haemopoietic differentiation or in the expression of differentiated cell character in myeloid cells.
Authors:
P J French; C M Bunce; L R Stephens; J M Lord; F M McConnell; G Brown; J A Creba; R H Michell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings. Biological sciences / The Royal Society     Volume:  245     ISSN:  0962-8452     ISO Abbreviation:  Proc. Biol. Sci.     Publication Date:  1991 Sep 
Date Detail:
Created Date:  1992-01-15     Completed Date:  1992-01-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101245157     Medline TA:  Proc Biol Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  193-201     Citation Subset:  IM    
Affiliation:
School of Biochemistry, University of Birmingham, U.K.
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MeSH Terms
Descriptor/Qualifier:
Cell Differentiation / drug effects
Dimethyl Sulfoxide / pharmacology
Humans
Inositol / metabolism*
Inositol Phosphates / metabolism*
Leukemia, Promyelocytic, Acute / metabolism*,  pathology
Lipid Metabolism
Monocytes / drug effects,  metabolism,  pathology
Neutrophils / drug effects,  metabolism,  pathology
Tetradecanoylphorbol Acetate / pharmacology
Tumor Cells, Cultured / drug effects,  metabolism,  pathology
Chemical
Reg. No./Substance:
0/Inositol Phosphates; 16561-29-8/Tetradecanoylphorbol Acetate; 67-68-5/Dimethyl Sulfoxide; 6917-35-7/Inositol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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