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Studies on the mechanism of action of hexamethylene bisacetamide, a potent inducer of erythroleukemic differentiation.

Authors :
Reuben RC
Source :
Biochimica et biophysica acta [Biochim Biophys Acta] 1979 Dec 11; Vol. 588 (3), pp. 310-21.
Publication Year :
1979

Abstract

Hexamethylene bisacetamide (diacetyldiamino hexane) is a potent inducer of erythroid differentiation in murine erythroleukemia cells. Hexamethylene bisacetamide and the closely related pentamethylene bisacetamide were synthesized with radioactive labels in various portions of the molecule and the uptake, metabolism, and intracellular distribution determined. Bisacetamides are taken up by the cell; an intracellular concentration equal to the extracellular concentration is achieved by 6-8 h. Commitment to differentiation is not detected until at least 10 h after equilibration. Both uptake and commitment to differentiate are concentration and temperature dependent. The majority of the compound is deacetylated upon cell entry and the acetate portion incorporated nonspecifically into lipid and protein. Acetate competes with the incorporation of hexamethylene bisacetamide into protein and lipid, but does not affect inducing activity. The diamine portion of the molecule is detected only in the cytoplasm, in a trichloroacetic acid-soluble and acetylated form, whereas the acetate moiety is detected in both cytoplasm and nucleus and in both a trichloroacetic acid-soluble and insoluble form. The cellular uptake of diamines and bisacetamides (acetylated diamines) are similar, but acetylation of the diamine greatly increases inducing activity.

Details

Language :
English
ISSN :
0006-3002
Volume :
588
Issue :
3
Database :
MEDLINE
Journal :
Biochimica et biophysica acta
Publication Type :
Academic Journal
Accession number :
292456
Full Text :
https://doi.org/10.1016/0304-4165(79)90339-8