Dimethyl sulphoxide and haemin induce ferrochelatase mRNA by different mechanisms in murine erythroleukaemia cells

Fukuda, Yoshiaki; Fujita, Hideaki; Taketani, Shigeru; Sassa, Shigeru

doi:10.1111/j.1365-2141.1993.tb04674.x

Cited by 21 publications

(18 citation statements)

References 35 publications

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“…The 5'-flanking region of the human ferrochelatase gene has binding sites for GATA-1 and NF-E2, and both erythroid-specific transcriptional factors may regulate the induction of ferrochelatase during erythroid differentiation. An increase of ferrochelatase mRNA in MEL cells is observed within 12h after the addition of DMSO, and parallells that of erythroid ALA synthase (Fukuda et al 1993). These inductions are earlier than those of mRNAs encoding other heme biosynthetic enzymes (Grandchamp et al 1985;Fujita et al 1991b).…”

Section: Location Of Ferrochelatase In Mitochondriamentioning

confidence: 99%

Molecular and Genetic Characterization of Ferrochelatase.

Taketani

1993

Tohoku J. Exp. Med.

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Section: Location Of Ferrochelatase In Mitochondriamentioning

confidence: 99%

Molecular and Genetic Characterization of Ferrochelatase.

Taketani

1993

Tohoku J. Exp. Med.

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“…The 5'-flanking region of the human ferrochelatase gene has binding sites for GATA-1 and NF-E2, and both erythroid-specific transcriptional factors may regulate the induction of ferrochelatase during erythroid differentiation. An increase of ferrochelatase mRNA in MEL cells is observed within 12 h after the addition of DMSO, and parallels that of erythroid ALA synthase [87]. These inductions are earlier than those of mRNA encoding other heme biosynthetic enzymes [55, 881.…”

Section: Regulation Of Ferrochelatase Synthesis During Erythroid Diffmentioning

confidence: 99%

Molecular and genetic characterization of ferrochelatase

Taketani

1994

Stem Cells

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Abstract. Ferrochelatase (heme synthase, protoheme ferrolyase [EC 4.99.1.1]), the final enzyme of the heme biosynthetic pathway, catalyzes the insertion of ferrous ion into protoporphyrin IX to produce protoheme IX. The thorough understanding of the enzyme is prerequisite to elucidating the regulation of iron and heme metabolism. The enzyme's activity is found on the inner mitochondria1 membrane of a variety of mammalian cells. The enzyme catalyzes the chelation not only of iron but also of divalent metal ions including cobalt and zinc, and the activity is affected by various metals and lipids. The molecular weights of eukaryotic ferrochelatases are 40,000-42,000 daltons. Complementary DNA (cDNA) encoding ferrochelatase from mouse, human, yeast and bacteria have been isolated, and the derived amino acid sequences show 27438% homologies among species. The expression of ferrochelatase seems to occur in all living cells, and to play an important role in the regulation of heme biosynthesis. Ferrochelatase is markedly induced at the transcriptional level during erythroid differentiation when iron uptake by cells and hemoglobin synthesis are upregulated. This induction can be explained by the existence of sequences characteristic of erythroid-related genes. The gene has been mapped to human chromosome 18q21.3 and contains 11 exons with a size of about 45 kilobases. Once the gene for human ferrochelatase is cloned, the molecular basis and clinical diagnosis of erythropoietic protoporphyria, caused by a deficiency of ferrochelatase, will become possible. This review summarizes recent advances in ferrochelatase research and suggests important subjects for future research.

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“…2 0 0 4 ) . Furthermore, the stability of ALAS1 mRNA and ferrochelatase mRNA is regulated by heme (Fujita et al 1991;Fukuda et al 1993). However, for a long time, the mechanisms involved in the hemedependent regulation of expression at the transcription level had not been understood.…”

Section: Heme-dependent Regulation Of Hemoprotein Biogenesismentioning

confidence: 99%

Aquisition, Mobilization and Utilization of Cellular Iron and Heme: Endless Findings and Growing Evidence of Tight Regulation

Taketani

2005

Tohoku J. Exp. Med.

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Iron is fastidiously utilized by living cells, since it is an essential element, but is toxic in excess. Cells take up iron via a transferrin-transferrin receptor-dependent endocytotic process. The iron thus taken up is used for essential biological functions including oxygen transport, electron transfer, and DNA synthesis. The intracellular level of iron is tightly controlled, through regulation of the cellular uptake of iron and the sequestering of low molecular labile iron into the storage protein ferritin. The known proteins of iron transport and storage, transferrin, transferrin receptor and ferritin, have been recently linked with a number of newly identified proteins that are responsible for inherited diseases of iron metabolisms and play critical roles in the maintenance of iron homeostasis. These proteins are involved in regulation of intracellular levels of iron, iron transport, and heme transport and the oxygen-dependent regulation of gene expression. On the other hand, most iron is transported into mitochondria and immediately used for the biosynthesis of heme in erythroid cells. The heme biosynthesis in mitochondria is coupled with the supply of iron, and the heme, exported from mitochondria, is utilized as prosthetic groups of hemeproteins. Furthermore, non-erythroid and erythroid cells possess the different regulatory systems for the biosynthesis of heme; iron positively regulates the biosynthesis in erythroid cells while heme negatively regulates it in non-erythroid cells. Because of the toxicity and insolubility of heme, the intracellular level of uncommitted heme is maintained at a low concentration (< 10 -9 M). The influx and efflux of heme also help to prevent cytotoxicity. Finally, heme-binding transcriptional factors such as Bach1 and NPAS2 regulate the transcription of several genes involved in the synthesis and degradation of heme-hemeproteins. The discovery of new molecules related to disorders of iron and heme metabolism is ascribable to a complete mechanistic understanding of the cellular network of iron homeostasis. The network of interactions that link iron and heme metabolisms with functions of cellular regulation involving oxidative stress and inflammations contributes to new insights into clinical aspects of disorders.

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Dimethyl sulphoxide and haemin induce ferrochelatase mRNA by different mechanisms in murine erythroleukaemia cells

Cited by 21 publications

References 35 publications

Molecular and Genetic Characterization of Ferrochelatase.

Molecular and Genetic Characterization of Ferrochelatase.

Molecular and genetic characterization of ferrochelatase

Aquisition, Mobilization and Utilization of Cellular Iron and Heme: Endless Findings and Growing Evidence of Tight Regulation

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