Detail of "51568-18-4"

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Augmentation of hematoporphyrin uptake and in vitro-growth inhibition of L1210 leukemia cells by succinylacetone

Augmentation of hematoporphyrin uptake and in vitro-growth inhibition of L1210 leukemia cells by succinylacetone. Ebert, Paul S.; Hess, Richard A.; Tschudy, Donald P. (Div. Cancer Etiol., Natl. Cancer Inst., Frederick, MD 21701, USA). JNCI, J. Natl. Cancer Inst., 74(3), 603-8 (English) 1985. CODEN: JJIND8. ISSN: 0198-0157. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Succinylacetone [51568-18-4] (SA), a specific inhibitor of d-aminolevulinic acid dehydrase (ALAD) [9036-37-7] (the 2nd enzyme of the heme biosynthetic pathway), was tested for its effect on L1210 cells from inbred DBA/2 mice. ALAD from broken L1210 cells was completely inhibited by 1 mM SA, but in whole cells activity was decreased only 83% after incubation of the cells with 2.5 mM SA for 3 days. When incubated with hematoporphyrin (HP) [14459-29-1], L1210 cells rapidly took up porphyrin from the medium, and this uptake could be augmented by pretreatment of the cells with SA; but this enhancement of porphyrin uptake occurred gradually over a period of days. When SA-treated and untreated L1210 cells were incubated with increasing concns. of HP in the medium, SA-treated cells reached the satn. concn. of cellular porphyrin at lower medium HP concns. than did untreated cells. Growth of L1210 cells could be inhibited by 32 mM SA. Addn. of increasing amts. of serum to cultures of cells contg. SA did not reverse the growth inhibition due to SA. Porphyrin uptake from HP in the medium in nonmalignant fibroblast line 3T3 was much lower than that in L1210 cells and could not be enhanced by incubation of the cells with SA.

Heme-dependent up-regulation of the a-globin gene expression by transcriptional repressor Bach1 in erythroid cells

Heme-dependent up-regulation of the a-globin gene expression by transcriptional repressor Bach1 in erythroid cells. Tahara, Tsuyoshi; Sun, Jiying; Igarashi, Kazuhiko; Taketani, Shigeru ( Department of Biotechnology, Kyoto Institute of Technology, Kyoto 606-8585, Japan). Biochemical and Biophysical Research Communications, 324(1), 77-85 (English) 2004 Elsevier. CODEN: BBRCA9. ISSN: 0006-291X. DOCUMENT TYPE: Journal CA Section: 3 (Biochemical Genetics) Section cross-reference(s): 13 The transcriptional factor Bach1 forms a heterodimer with small Maf family, and functions as a repressor of the Maf recognition element (MARE) in vivo. To investigate the involvement of Bach1 in the heme-dependent regulation of the expression of the a-globin gene, human erythroleukemia K562 cells were cultured with succinylacetone (SA), a heme biosynthetic inhibitor, and the level of a-globin mRNA was examd. A decrease of a-globin mRNA was obsd. in SA-treated cells, which was restored by the addn. of hemin. The heme-dependent expression of a-globin occurred at the transcriptional level since the expression of human a-globin gene promoter-reporter gene contg. hypersensitive site-40 (HS-40) was decreased when K562 cells were cultured with SA. Hemin treatment restored the decrease of the promoter activity by SA. The regulation of the HS-40 activity by heme was dependent on the NF-E2/AP-1 (NA) site, which is similar to MARE. The NA site-binding activity of Bach1 in K562 increased upon SA-treatment, and the increase was diminished by the addn. of hemin. The transient expression of Bach1 and mutated Bach1 lacking CP motifs suppressed the HS-40 activity, and cancellation of the repressor activity by hemin was obsd. when wild-type Bach1 was expressed.In this experiment, several chemicals are used like 14875-96-8 and 51568-18-4 The expression of NF-E2 strengthened the restoration of the Bach1-effect by hemin. Interestingly, nuclear localization of Bach1 increased when cells were treated with SA, while hemin induced the nuclear export of Bach1. These results indicated that heme plays an important role in the induction of a-globin gene expression through disrupting the interaction of Bach1 and the NA site in HS-40 enhancer in erythroid cells. .