Regulation of 5-aminolevulinate synthase in mouse erythroleukemic cells is different from that in liver

• Published in: The Journal of biological chemistry Vol. 263; no. 26; pp. 13012 - 13016
• Main Authors: Elferink, C J, Sassa, S, May, B K
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 15.09.1988; American Society for Biochemistry and Molecular Biology
• Subjects: 5-aminolevulinate synthase; 5-Aminolevulinate Synthetase - genetics; 5-Aminolevulinate Synthetase - metabolism; Animals; Biological and medical sciences; erythroleukemia; Fundamental and applied biological sciences. Psychology; Hemin - pharmacology; Heptanoates - pharmacology; Leukemia, Erythroblastic, Acute - enzymology; liver; Liver - enzymology; Mice; Molecular and cellular biology; Molecular genetics; RNA, Messenger - metabolism; Transcription, Genetic - drug effects; Transcription. Transcription factor. Splicing. Rna processing; Cell culture; Molecular hybridization; Transcription; Enzyme; Leukemia; Rodentia; Cell differentiation; Posttranscriptional modification; δ-Aminolaevulinate synthase; Vertebrata; Regulation(control); Mammalia; Mouse
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)37664-6

We have measured the transcriptional gene activity of 5-aminolevulinate synthase, the first enzyme of the heme biosynthetic pathway, together with corresponding mRNA and protein levels in mouse erythroleukemic cells induced to differentiate with dimethyl sulfoxide. When the heme biosynthetic pathway was blocked by succinylacetone there was a large increase in both 5-aminolevulinate synthase activity and protein levels, and this was reversed by the addition of exogenous hemin. Transcriptional activity of the 5-aminolevulinate synthase gene and mRNA levels were both significantly increased during differentiation of cells by dimethyl sulfoxide but were not markedly altered by succinylacetone or hemin treatment. The results demonstrate that levels of 5-aminolevulinate synthase in mouse erythroleukemic cells are regulated by a significant post-transcriptional mechanism possibly at the translational level. Evidence is also presented for a less significant post-transcriptional control by heme of mRNA levels for 5-aminolevulinate synthase. These results indicate that the regulation of 5-aminolevulinate synthase in differentiating erythroid cells is complex but differs from that in liver cells where heme controls the level of 5-aminolevulinate synthase by acting primarily to inhibit gene transcription.