TY - JOUR
T1 - Siderocalin/Lcn2/NGAL/24p3 does not drive apoptosis through gentisic acid mediated iron withdrawal in hematopoietic cell lines
AU - Correnti, Colin
AU - Richardson, Vera
AU - Sia, Allyson K.
AU - Bandaranayake, Ashok D.
AU - Ruiz, Mario
AU - Rahmanto, Yohan Suryo
AU - Kovačević, Žaklina
AU - Clifton, Matthew C.
AU - Holmes, Margaret A.
AU - Kaiser, Brett K.
AU - Barasch, Jonathan
AU - Raymond, Kenneth N.
AU - Richardson, Des R.
AU - Strong, Roland K.
N1 - Funding Information:
Dr. Clifton is employed by a commercial company, “Emerald Biostructures”, but his participation in this project is solely through Emerald Biostructures role in the Seattle Structural Genomics Center for Infectious Diseases (SSGCID), which is funded through National Institute of Allergy and Infectious Disease Federal Contract No. HHSN272200700057C. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.
PY - 2012/8/21
Y1 - 2012/8/21
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0043696
DO - 10.1371/journal.pone.0043696
M3 - Article
C2 - 22928018
AN - SCOPUS:84865191769
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 8
M1 - e43696
ER -