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| http://purl.uniprot.org/citations/30448403 | http://www.w3.org/2000/01/rdf-schema#comment | "CYP46A1 is the cytochrome P450 enzyme that converts cholesterol to 24-hydroxycholesterol, a cholesterol elimination product and a potent liver X receptor (LXR) ligand. We conducted retinal characterizations of Cyp46a1-/- mice that had normal fasting blood glucose levels but up to a 1.8-fold increase in retinal cholesterol. The retina of Cyp46a1-/- mice exhibited venous beading and tortuosity, microglia/macrophage activation, and increased vascular permeability, features commonly associated with diabetic retinopathy. The expression of Lxrα and Lxrβ was increased in both the whole Cyp46a1-/- retina and retinal macroglia/macrophages. The LXR-target genes were affected as well, primarily in activated microglial cells and macrophages. In the latter, the LXR-transactivated genes (Abca1, Abcg1, Apod, Apoe, Mylip, and Arg2) were up-regulated; similarly, there was an up-regulation of the LXR-transrepressed genes (Ccl2, Ptgs2, Cxcl1, Il1b, Il6, Nos2, and Tnfa). For comparison, gene expression was investigated in bone marrow-derived macrophages from Cyp46a1-/- mice as well as retinal and bone marrow-derived macrophages from Cyp27a1-/- and Cyp27a1-/-Cyp46a1-/- mice. CYP46A1 expression was detected in retinal endothelial cells, and this expression was increased in the proinflammatory environment. Retinal Cyp46a1-/- phosphoproteome revealed altered phosphorylation of 30 different proteins, including tight junction protein zonula occludens 1 and aquaporin 4. Collectively, the data obtained establish metabolic and regulatory significance of CYP46A1 for the retina and suggest pharmacologic activation of CYP46A1 as a potential therapeutic approach to dyslipidemia-induced retinal damage."xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajpath.2018.10.013"xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/author | "Pikuleva I.A."xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/author | "Mast N."xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/author | "Hammer S."xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/author | "Busik J.V."xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/author | "Grant M.B."xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/author | "Chakraborty D."xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/author | "Saadane A."xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/author | "Trichonas G."xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/name | "Am J Pathol"xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/pages | "405-425"xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/title | "Retinal Vascular Abnormalities and Microglia Activation in Mice with Deficiency in Cytochrome P450 46A1-Mediated Cholesterol Removal."xsd:string |
| http://purl.uniprot.org/citations/30448403 | http://purl.uniprot.org/core/volume | "189"xsd:string |
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