| Haem precursor delta-aminolaevulinic acid induces activation of the cytosolic iron regulatory protein 1. | |
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MedLine Citation:
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PMID: 9396727 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Control of cellular iron homoeostasis is performed by iron regulatory protein 1 (IRP1) through post-transcriptional modifications. This protein is sensitive to intracellular iron availability, being activated at low iron levels and inactivated at high iron levels, conditions that signal the increased expression of the transferrin receptor or of ferritin respectively. IRP1 is known to be activated by some oxidants such as H2O2 and NO. delta-Aminolaevulinic acid (ALA), previously found to produce reactive oxygen species and a carbon-centred radical, to release iron from ferritin, and to increase rat liver and brain non-haem iron and ferritin, was investigated for its effects on IRP1 activity in cultured hamster pulmonary fibroblasts. We have found that 1-2 mM ALA produced a 2-3-fold activation of IRP. On incubation with 1-4 mM succinylacetone methyl ester, a potent ALA dehydratase inhibitor, a 3-4-fold activation of the protein was observed, accompanied by a 40% increase in the intracellular ALA concentration. When cells were incubated in the presence of ALA or succinylacetone methyl ester, N-acetylcysteine inhibited IRP1 activation, suggesting that the observed effect is mediated by an oxidative process. We surmise that ALA-induced IRP1 activation might act as a co-sensor of iron homoeostasis. |
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Authors:
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H Carvalho; E J Bechara; R Meneghini; M Demasi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 328 ( Pt 3) ISSN: 0264-6021 ISO Abbreviation: Biochem. J. Publication Date: 1997 Dec |
Date Detail:
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Created Date: 1998-02-02 Completed Date: 1998-02-02 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 827-32 Citation Subset: IM |
Affiliation:
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Instituto de Qu approximately ímica, Universidade de São Paulo, CP 26077, 05599-970 São Paulo, SP, Brasil. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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pharmacology Aminolevulinic Acid / metabolism, pharmacology* Animals Cell Line Cricetinae Electrophoresis, Polyacrylamide Gel Enzyme Inhibitors / pharmacology Ferritins / genetics Heme / metabolism Homeostasis / physiology Iron / pharmacology Iron Regulatory Protein 1 Iron-Regulatory Proteins Iron-Sulfur Proteins / metabolism* Lung Oxidation-Reduction Porphobilinogen Synthase / antagonists & inhibitors RNA, Messenger / genetics, metabolism RNA-Binding Proteins / metabolism* Reactive Oxygen Species / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Iron-Regulatory Proteins; 0/Iron-Sulfur Proteins; 0/RNA, Messenger; 0/RNA-Binding Proteins; 0/Reactive Oxygen Species; 106-60-5/Aminolevulinic Acid; 14875-96-8/Heme; 616-91-1/Acetylcysteine; 7439-89-6/Iron; 9007-73-2/Ferritins; EC 4.2.1.24/Porphobilinogen Synthase; EC 4.2.1.3/Iron Regulatory Protein 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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