Document Detail


Haem precursor delta-aminolaevulinic acid induces activation of the cytosolic iron regulatory protein 1.
MedLine Citation:
PMID:  9396727     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
H Carvalho; E J Bechara; R Meneghini; M Demasi
Related Documents :
17622797 - Beclin 1-independent pathway of damage-induced mitophagy and autophagic stress: implica...
22864587 - Pyruvate kinase activity and δ-aminolevulinic acid dehydratase activity as biomarkers ...
22406317 - Superoxide plays critical roles in electrotaxis of fibrosarcoma cells via activation of...
20698827 - Impairment of f1f0-atpase, adenine nucleotide translocator and adenylate kinase causes ...
7905287 - Ultraviolet radiation induces differential calcium signals in human peripheral blood ly...
16317387 - Macrophage migration inhibitory factor within the alveolar spaces induces changes in th...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  328 ( Pt 3)     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-02-02     Completed Date:  1998-02-02     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  827-32     Citation Subset:  IM    
Affiliation:
Instituto de Qu approximately ímica, Universidade de São Paulo, CP 26077, 05599-970 São Paulo, SP, Brasil.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / 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:
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


Previous Document:  Characterization of a Drosophila phosphorylation-dependent nuclear-localization-signal-binding prote...
Next Document:  Covalent complex of microperoxidase with a 21-residue synthetic peptide as a maquette for low-molecu...