Document Detail


Siderocalin/Lcn2/NGAL/24p3 does not drive apoptosis through gentisic acid mediated iron withdrawal in hematopoietic cell lines.
MedLine Citation:
PMID:  22928018     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Siderocalin (also lipocalin 2, NGAL or 24p3) binds iron as complexes with specific siderophores, which are low molecular weight, ferric ion-specific chelators. In innate immunity, siderocalin slows the growth of infecting bacteria by sequestering bacterial ferric siderophores. Siderocalin also binds simple catechols, which can serve as siderophores in the damaged urinary tract. Siderocalin has also been proposed to alter cellular iron trafficking, for instance, driving apoptosis through iron efflux via BOCT. An endogenous siderophore composed of gentisic acid (2,5-dihydroxybenzoic acid) substituents was proposed to mediate cellular efflux. However, binding studies reported herein contradict the proposal that gentisic acid forms high-affinity ternary complexes with siderocalin and iron, or that gentisic acid can serve as an endogenous siderophore at neutral pH. We also demonstrate that siderocalin does not induce cellular iron efflux or stimulate apoptosis, questioning the role siderocalin plays in modulating iron metabolism.
Authors:
Colin Correnti; Vera Richardson; Allyson K Sia; Ashok D Bandaranayake; Mario Ruiz; Yohan Suryo Rahmanto; Žaklina Kovačević; Matthew C Clifton; Margaret A Holmes; Brett K Kaiser; Jonathan Barasch; Kenneth N Raymond; Des R Richardson; Roland K Strong
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-21
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-08-28     Completed Date:  2013-01-29     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e43696     Citation Subset:  IM    
Affiliation:
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Acute-Phase Proteins / chemistry,  pharmacology*
Animals
Apoptosis / drug effects*
Cell Survival / drug effects
Gentisates / metabolism*
HeLa Cells
Hematopoiesis*
Humans
Iron / metabolism*
Lipocalins / chemistry,  pharmacology*
Mice
Models, Molecular
Protein Conformation
Proto-Oncogene Proteins / chemistry,  pharmacology*
Grant Support
ID/Acronym/Agency:
AI117448/AI/NIAID NIH HHS; AI59432/AI/NIAID NIH HHS; DK55388/DK/NIDDK NIH HHS; DK58872/DK/NIDDK NIH HHS; HHSN272200700057C//PHS HHS; R01 AI011744/AI/NIAID NIH HHS; R01 DK073462/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Acute-Phase Proteins; 0/Gentisates; 0/LCN2 protein, human; 0/Lipocalins; 0/Proto-Oncogene Proteins; 7439-89-6/Iron; VP36V95O3T/2,5-dihydroxybenzoic acid
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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