Effects of succinylacetone on dimethylsulfoxide-mediated induction of heme pathway enzymes in mouse friend virus-transformed erythroleukemia cells.
Heme has been reported to exert a control over its own biosynthesis and to affect the erythroid differentiation process at different sites. In this study, succinylacetone, a powerful inhibitor of delta-aminolevulinic acid dehydrase was used to block heme synthesis and to study the effects of heme depletion on the dimethylsulfoxide (DMSO)-mediated induction of the heme pathway enzymes in Friend virus-transformed erythroleukemia cells. The presence of succinylacetone in the medium during the DMSO treatment (1) potentiates the induction of delta-aminolevulinic acid synthetase (the first enzyme of the pathway) and this effect is reversed by the addition of exogenous hemin; (2) does not affect the induction of delta-aminolevulinic acid dehydrase (the second enzyme); (3) prevents the induction of porphobilinogen deaminase (the third enzyme), since no increase could be detected in either the enzyme activity or the immunoreactive protein and this effect could not be reversed by the addition of exogenous hemin; (4) does not affect the induction of ferrochelatase. The possible role of heme or of intermediate metabolites of the pathway on the induction of these enzymes during the erythroid differentiation process is discussed.
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis; D000818:Animals; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005622:Friend murine leukemia virus; D006418:Heme / Q000096:biosynthesis*; D006427:Hemin / Q000494:pharmacology; D006454:Hemoglobins / Q000032:analysis; D006537:Heptanoates / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D011163:Hydroxymethylbilane Synthase / Q000096:biosynthesis; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D000623:Porphobilinogen Synthase / Q000096:biosynthesis
D006454:Hemoglobins; D006537:Heptanoates; D006538:Heptanoic Acids; D006418:Heme; C020804:succinylacetone; D006427:Hemin; D000624:5-Aminolevulinate Synthetase; D011163:Hydroxymethylbilane Synthase; D000623:Porphobilinogen Synthase; D004121:Dimethyl Sulfoxide