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Siderocalin/Lcn2/NGAL/24p3 Does Not Drive Apoptosis Through Gentisic Acid Mediated Iron Withdrawal in Hematopoietic Cell Lines

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
7
Issue
8
Identifiers
DOI: 10.1371/journal.pone.0043696
Keywords
  • Research Article
  • Biology
  • Biochemistry
  • Metabolism
  • Biological Transport
  • Metabolic Pathways
  • Proteins
  • Acute Phase Proteins
  • Defense Proteins
  • Immune System Proteins
  • Plasma Proteins
  • Protein Chemistry
  • Protein Interactions
  • Protein Structure
  • Biomacromolecule-Ligand Interactions
  • Small Molecules
  • Biophysics
  • Microbiology
  • Immunity
  • Innate Immunity
  • Host-Pathogen Interaction
  • Molecular Cell Biology
  • Cell Death

Abstract

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.

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