| http://purl.uniprot.org/citations/28478229 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28478229 | http://www.w3.org/2000/01/rdf-schema#comment | "In diabetes, matrix metalloproteinase-9 (MMP-9) is activated, which damages mitochondria, resulting in accelerated capillary cell apoptosis. Regulation of MMP-9 is controlled by multiple transcription factors including nuclear factor-kB (NF-kB) and activator protein-1 (AP-1). Binding of these transcription factors, however, can be regulated by poly(ADP-ribose) polymerase-1 (PARP-1), which forms a strong initiation complex at the promoter region and facilitates multiple rounds of gene transcription. This complex formation with the transcription factors is regulated by posttranslational acetylation of PARP-1, and in diabetes, the deacetylating enzyme, Sirt1, is inhibited. Our aim was to understand the role of PARP-1 in transcriptional regulation of MMP-9 in the development of diabetic retinopathy. Using human retinal endothelial cells, the effect of PARP-1 inhibition (pharmacologically by PJ34, 1μM; or genetically by its siRNA) on MMP-9 expression was investigated. The effect of PARP-1 acetylation on its binding at the MMP-9 promoter, and with NF-kB/AP-1, was investigated in the cells transfected with Sirt1. In vitro results were validated in the retinal microvessels from diabetic mice either administered PJ34, or overexpressing Sirt1. Inhibition of PARP-1 ameliorated hyperglycemia-induced increase in the binding of NF-kB/AP-1 at the MMP-9 promoter, decreased MMP-9 expression and ameliorated mitochondrial damage. Overexpression of Sirt1 attenuated diabetes-induced increase in PARP-1 binding at MMP-9 promoter or with NF-kB/AP-1. Thus, PARP-1, via manipulating the binding of NF-kB/AP-1 at the MMP-9 promoter, regulates MMP-9 expression, which helps maintain mitochondrial homeostasis."xsd:string |
| http://purl.uniprot.org/citations/28478229 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bbadis.2017.04.024"xsd:string |
| http://purl.uniprot.org/citations/28478229 | http://purl.uniprot.org/core/author | "Mishra M."xsd:string |
| http://purl.uniprot.org/citations/28478229 | http://purl.uniprot.org/core/author | "Kowluru R.A."xsd:string |
| http://purl.uniprot.org/citations/28478229 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28478229 | http://purl.uniprot.org/core/name | "Biochim Biophys Acta Mol Basis Dis"xsd:string |
| http://purl.uniprot.org/citations/28478229 | http://purl.uniprot.org/core/pages | "1761-1769"xsd:string |
| http://purl.uniprot.org/citations/28478229 | http://purl.uniprot.org/core/title | "Role of PARP-1 as a novel transcriptional regulator of MMP-9 in diabetic retinopathy."xsd:string |
| http://purl.uniprot.org/citations/28478229 | http://purl.uniprot.org/core/volume | "1863"xsd:string |
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