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http://purl.uniprot.org/citations/27607416http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27607416http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

Accumulation of oxidized phospholipids/lipoproteins with age is suggested to contribute to the pathogenesis of AMD. We investigated the effect of oxidized LDL (ox-LDL) on human RPE cells.

Methods

Primary human fetal RPE (hf-RPE) and ARPE-19 cells were treated with different doses of LDL or ox-LDL. Assessment of cell death was measured by lactate dehydrogenase release into the conditioned media. Barrier function of RPE was assayed by measuring transepithelial resistance. Lysosomal accumulation of ox-LDL was determined by immunostaining. Expression of CD36 was determined by RT-PCR; protein blot and function was examined by receptor blocking. NLRP3 inflammasome activation was assessed by RT-PCR, protein blot, caspase-1 fluorescent probe assay, and inhibitor assays.

Results

Treatment with ox-LDL, but not LDL, for 48 hours caused significant increase in hf-RPE and ARPE-19 (P < 0.001) cell death. Oxidized LDL treatment of hf-RPE cells resulted in a significant decrease in transepithelial resistance (P < 0.001 at 24 hours and P < 0.01 at 48 hours) relative to LDL-treated and control cells. Internalized ox-LDL was targeted to RPE lysosomes. Uptake of ox-LDL but not LDL significantly increased CD36 protein and mRNA levels by more than 2-fold. Reverse transcription PCR, protein blot, and caspase-1 fluorescent probe assay revealed that ox-LDL treatment induced NLRP3 inflammasome when compared with LDL treatment and control. Inhibition of NLRP3 activation using 10 μM isoliquiritigenin significantly (P < 0.001) inhibited ox-LDL induced cytotoxicity.

Conclusions

These data are consistent with the concept that ox-LDL play a role in the pathogenesis of AMD by NLRP3 inflammasome activation. Suppression of NLRP3 inflammasome activation could attenuate RPE degeneration and AMD progression."xsd:string
http://purl.uniprot.org/citations/27607416http://purl.org/dc/terms/identifier"doi:10.1167/iovs.15-18663"xsd:string
http://purl.uniprot.org/citations/27607416http://purl.uniprot.org/core/author"Choi A.R."xsd:string
http://purl.uniprot.org/citations/27607416http://purl.uniprot.org/core/author"D'Amore P.A."xsd:string
http://purl.uniprot.org/citations/27607416http://purl.uniprot.org/core/author"Gnanaguru G."xsd:string
http://purl.uniprot.org/citations/27607416http://purl.uniprot.org/core/author"Amarnani D."xsd:string
http://purl.uniprot.org/citations/27607416http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27607416http://purl.uniprot.org/core/name"Invest Ophthalmol Vis Sci"xsd:string
http://purl.uniprot.org/citations/27607416http://purl.uniprot.org/core/pages"4704-4712"xsd:string
http://purl.uniprot.org/citations/27607416http://purl.uniprot.org/core/title"Oxidized Lipoprotein Uptake Through the CD36 Receptor Activates the NLRP3 Inflammasome in Human Retinal Pigment Epithelial Cells."xsd:string
http://purl.uniprot.org/citations/27607416http://purl.uniprot.org/core/volume"57"xsd:string
http://purl.uniprot.org/citations/27607416http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27607416
http://purl.uniprot.org/citations/27607416http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27607416
http://purl.uniprot.org/uniprot/P16671#attribution-1FF85B1AF20B517BA76BB373F762E2C1http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/27607416