Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 87, Issue -, Pages 43-59Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2015.04.009
Keywords
Siderophore; Lipocalins; Lipocalin 2; Megalin; BOCT; Bim; Apoptosis; Iron; Neurodegeneration
Categories
Funding
- National Medical Research Council of Singapore [NMRC/EDG/1021/2010]
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The iron siderophore binding protein lipocalin 2 (LCN2, also known as 24p3, NGAL and siderocalin) may be involved in iron homeostasis, but to date, little is known about expression of its putative receptor, brain-type organic cation transporter (BOCT, also known as BOCT1, 24p3R, NGALR and LCN2R), in the brain during neurodegeneration. The present study was carried out to elucidate the expression of LCN2 and BOCT in hippocampus after excitotoxicity induced by the glutamate analog, kainate (KA) and a possible role of LCN2 in neuronal injury. As reported previously, a rapid and sustained induction in expression of LCN2 was found in the hippocampus after intracerebroventicular injection of KA. BOCT was expressed in neurons of the saline-injected control hippocampus, and immunolabel for BOCT protein was preserved in pyramidal neurons of CA1 at 1 day post-MA injection, likely due to the delayed onset of neurodegeneration after MA injection. At 3 days and 2 weeks after MA injections, loss of immunolabel was observed due to degenerated neurons, although remaining neurons continued to express BOCT, and induction of BOCT was found in OX-42 positive microglia. This resulted in an overall decrease in BOCT mRNA and protein expression after MA treatment. Increased expression of the pro-apoptotic marker, Bim, was found in both neurons and microglia after MA injection, but TUNEL staining indicating apoptosis was found primarily in Bim-expressing neurons, but not microglia. Interaction between LCN2 and BOCT was found by DuoLink assay in cultured hippocampal neurons. Apo-LCN2 without iron caused no significant differences in neuronal Bim expression or cell survival, whereas holo-LCN2 consisting of LCN2:iron:enterochelin complex increased Bim mRNA expression and decreased neuronal survival. Together, results suggest that LCN2 and BOCT may have a role in neuronal injury. (C) 2015 Elsevier Ltd. All rights reserved.
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