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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2010-4-23
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pubmed:abstractText |
alphaB-crystallin is a chaperone belonging to the small heat shock protein family. Herein we show attenuation of intraocular angiogenesis in alphaB-crystallin knockout (alphaB-crystallin(-/-)) mice in 2 models of intraocular disease: oxygen-induced retinopathy and laser-induced choroidal neovascularization. Vascular endothelial growth factor A (VEGF-A) mRNA and hypoxia inducible factor-1alpha protein expression were induced during retinal angiogenesis, but VEGF-A protein expression remained low in alphaB-crystallin(-/-) retina versus wild-type mice, whereas VEGF-R2 expression was not affected. Both alphaB-crystallin and its phosphorylated serine59 formwere expressed, and immunoprecipitation revealed alphaB-crystallin binding to VEGF-A but not transforming growth factor-beta in cultured retinal pigment epithelial (RPE) cells. alphaB-crystallin and VEGF-A are colocalized in the endoplasmic reticulum in RPE cells under chemical hypoxia. alphaB-crystallin(-/-) RPE showed low VEGF-A secretion under serum-starved conditions compared with wild-type cells. VEGF-A is polyubiquitinated in control and alphaB-crystallin siRNA treated RPE; however, mono-tetra ubiquitinated VEGF-A increases with alphaB-crystallin knockdown. Endothelial cell apoptosis in newly formed vessels was greater in alphaB-crystallin(-/-) than wild-type mice. Proteasomal inhibition in alphaB-crystallin(-/-) mice partially restores VEGF-A secretion and angiogenic phenotype in choroidal neovascularization. Our studies indicate an important role for alphaB-crystallin as a chaperone for VEGF-A in angiogenesis and its potential as a therapeutic target.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1528-0020
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
115
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3398-406
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pubmed:dateRevised |
2011-7-28
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pubmed:meshHeading |
pubmed-meshheading:20023214-Animals,
pubmed-meshheading:20023214-Apoptosis,
pubmed-meshheading:20023214-Blotting, Western,
pubmed-meshheading:20023214-Choroidal Neovascularization,
pubmed-meshheading:20023214-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:20023214-Gene Expression,
pubmed-meshheading:20023214-Humans,
pubmed-meshheading:20023214-Immunohistochemistry,
pubmed-meshheading:20023214-Immunoprecipitation,
pubmed-meshheading:20023214-In Situ Nick-End Labeling,
pubmed-meshheading:20023214-Mice,
pubmed-meshheading:20023214-Mice, Knockout,
pubmed-meshheading:20023214-Retinal Pigment Epithelium,
pubmed-meshheading:20023214-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20023214-Vascular Endothelial Growth Factor A,
pubmed-meshheading:20023214-alpha-Crystallin B Chain
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pubmed:year |
2010
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pubmed:articleTitle |
alphaB-crystallin regulation of angiogenesis by modulation of VEGF.
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pubmed:affiliation |
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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pubmed:publicationType |
Journal Article
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