RGD Reference Report - A potential neuroprotective role of apolipoprotein E-containing lipoproteins through low density lipoprotein receptor-related protein 1 in normal tension glaucoma. - Rat Genome Database

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A potential neuroprotective role of apolipoprotein E-containing lipoproteins through low density lipoprotein receptor-related protein 1 in normal tension glaucoma.

Authors: Hayashi, Hideki  Eguchi, Yuko  Fukuchi-Nakaishi, Yuko  Takeya, Motohiro  Nakagata, Naomi  Tanaka, Kohichi  Vance, Jean E  Tanihara, Hidenobu 
Citation: Hayashi H, etal., J Biol Chem. 2012 Jul 20;287(30):25395-406. doi: 10.1074/jbc.M112.370130. Epub 2012 Jun 6.
RGD ID: 13800523
Pubmed: PMID:22674573   (View Abstract at PubMed)
PMCID: PMC3408193   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M112.370130   (Journal Full-text)

Glaucoma is an optic neuropathy and the second major cause of blindness worldwide next to cataracts. The protection from retinal ganglion cell (RGC) loss, one of the main characteristics of glaucoma, would be a straightforward treatment for this disorder. However, the clinical application of neuroprotection has not, so far, been successful. Here, we report that apolipoprotein E-containing lipoproteins (E-LPs) protect primary cultured RGCs from Ca(2+)-dependent, and mitochondrion-mediated, apoptosis induced by glutamate. Binding of E-LPs to the low density lipoprotein receptor-related protein 1 recruited the N-methyl-d-aspartate receptor, blocked intracellular Ca(2+) elevation, and inactivated glycogen synthase kinase 3ß, thereby inhibiting apoptosis. When compared with contralateral eyes treated with phosphate-buffered saline, intravitreal administration of E-LPs protected against RGC loss in glutamate aspartate transporter-deficient mice, a model of normal tension glaucoma that causes glaucomatous optic neuropathy without elevation of intraocular pressure. Although the presence of α2-macroglobulin, another ligand of the low density lipoprotein receptor-related protein 1, interfered with the neuroprotective effect of E-LPs against glutamate-induced neurotoxicity, the addition of E-LPs overcame the inhibitory effect of α2-macroglobulin. These findings may provide a potential therapeutic strategy for normal tension glaucoma by an LRP1-mediated pathway.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Lrp1Ratnegative regulation of cytosolic calcium ion concentration  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lrp1  (LDL receptor related protein 1)


Additional Information