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| pubmed-article:19805546 | lifeskim:mentions | umls-concept:C0205093 | lld:lifeskim |
| pubmed-article:19805546 | lifeskim:mentions | umls-concept:C0033684 | lld:lifeskim |
| pubmed-article:19805546 | lifeskim:mentions | umls-concept:C0221099 | lld:lifeskim |
| pubmed-article:19805546 | lifeskim:mentions | umls-concept:C1420306 | lld:lifeskim |
| pubmed-article:19805546 | lifeskim:mentions | umls-concept:C0596988 | lld:lifeskim |
| pubmed-article:19805546 | lifeskim:mentions | umls-concept:C1514248 | lld:lifeskim |
| pubmed-article:19805546 | lifeskim:mentions | umls-concept:C0388204 | lld:lifeskim |
| pubmed-article:19805546 | lifeskim:mentions | umls-concept:C1414371 | lld:lifeskim |
| pubmed-article:19805546 | lifeskim:mentions | umls-concept:C1420731 | lld:lifeskim |
| pubmed-article:19805546 | lifeskim:mentions | umls-concept:C1171892 | lld:lifeskim |
| pubmed-article:19805546 | pubmed:issue | 49 | lld:pubmed |
| pubmed-article:19805546 | pubmed:dateCreated | 2009-11-30 | lld:pubmed |
| pubmed-article:19805546 | pubmed:abstractText | Down-regulation of vascular endothelial growth factor (VEGF) in the mouse leads to progressive and selective degeneration of motor neurons similar to amyotrophic lateral sclerosis (ALS). In mice expressing ALS-associated mutant superoxide dismutase 1 (SOD1), VEGF mRNA expression in the spinal cord declines significantly prior to the onset of clinical manifestations. In vitro models suggest that dysregulation of VEGF mRNA stability contributes to that decline. Here, we show that the major RNA stabilizer, Hu Antigen R (HuR), and TIA-1-related protein (TIAR) colocalize with mutant SOD1 in mouse spinal cord extracts and cultured glioma cells. The colocalization was markedly reduced or abolished by RNase treatment. Immunoanalysis of transfected cells indicated that colocalization occurred in insoluble aggregates and inclusions. RNA immunoprecipitation showed a significant loss of VEGF mRNA binding to HuR and TIAR in mutant SOD1 cells, and there was marked depletion of HuR from polysomes. Ectopic expression of HuR in mutant SOD1 cells more than doubled the mRNA half-life of VEGF and significantly increased expression to that of wild-type SOD1 control. Cellular effects produced by mutant SOD1, including impaired mitochondrial function and oxidative stress-induced apoptosis, were reversed by HuR in a gene dose-dependent pattern. In summary, our findings indicate that mutant SOD1 impairs post-transcriptional regulation by sequestering key regulatory RNA-binding proteins. The rescue effect of HuR suggests that this impairment, whether related to VEGF or other potential mRNA targets, contributes to cytotoxicity in ALS. | lld:pubmed |
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| pubmed-article:19805546 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:19805546 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:19805546 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19805546 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:19805546 | pubmed:issn | 1083-351X | lld:pubmed |
| pubmed-article:19805546 | pubmed:author | pubmed-author:NaborsL BLB | lld:pubmed |
| pubmed-article:19805546 | pubmed:author | pubmed-author:ZhengLeiL | lld:pubmed |
| pubmed-article:19805546 | pubmed:author | pubmed-author:LiangLuL | lld:pubmed |
| pubmed-article:19805546 | pubmed:author | pubmed-author:KingPeter HPH | lld:pubmed |
| pubmed-article:19805546 | pubmed:author | pubmed-author:WangShuyingS | lld:pubmed |
| pubmed-article:19805546 | pubmed:author | pubmed-author:WheelerCrysta... | lld:pubmed |
| pubmed-article:19805546 | pubmed:author | pubmed-author:ZhangXiaowenX | lld:pubmed |
| pubmed-article:19805546 | pubmed:author | pubmed-author:LiXuelinX | lld:pubmed |
| pubmed-article:19805546 | pubmed:author | pubmed-author:FilippovaNata... | lld:pubmed |
| pubmed-article:19805546 | pubmed:author | pubmed-author:SuswamEsther... | lld:pubmed |
| pubmed-article:19805546 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19805546 | pubmed:day | 4 | lld:pubmed |
| pubmed-article:19805546 | pubmed:volume | 284 | lld:pubmed |
| pubmed-article:19805546 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19805546 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19805546 | pubmed:pagination | 33989-98 | lld:pubmed |
| pubmed-article:19805546 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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| pubmed-article:19805546 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19805546 | pubmed:articleTitle | Amyotrophic lateral sclerosis-linked mutant SOD1 sequesters Hu antigen R (HuR) and TIA-1-related protein (TIAR): implications for impaired post-transcriptional regulation of vascular endothelial growth factor. | lld:pubmed |
| pubmed-article:19805546 | pubmed:affiliation | Department of Neurology, University of Alabama at Birmingham and the Birmingham Veterans Affairs Medical Center, Birmingham, Alabama 35294, USA. | lld:pubmed |
| pubmed-article:19805546 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:19805546 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:19805546 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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