Diabetic retinopathy and transcriptional regulation of a small molecular weight G-Protein, Rac1.
Exp Eye Res
; 147: 72-77, 2016 06.
Article
en En
| MEDLINE
| ID: mdl-27109029
ABSTRACT
In diabetic retinopathy, increased cytosolic reactive oxygen species, produced by NADPH oxidase (Nox), damage mitochondria, and this accelerates apoptosis of retinal capillary cells, resulting in the histopathology. Activation of Nox2 is mediated by a small molecular weight GTPase, Rac1, and retinal Rac1 is activated in diabetes. Our goal is to investigate the molecular mechanism responsible for transcriptional activation of Rac1 in the development of diabetic retinopathy. Using retinal microvessels, the site of histopathology associated with diabetic retinopathy, from streptozotocin-induced diabetic rats, we investigated the binding of the nuclear transcriptional factor-kB (NF-kB) at Rac1 promoter. Since activation of NF-kB is regulated by its acetylation-deacetylation, the role of acetylation in Rac1 transcription was confirmed in the retina from diabetic mice overexpressing a deacetylase, Sirtuin 1. Diabetes increased the binding of p65 subunit of NF-kB at the Rac1 promoter. Overexpression of Sirtuin 1 prevented hyper-acetylation of p65, decreased its binding at the Rac1 promoter and ameliorated Rac1-Nox2 mediated mitochondrial damage. Thus, in diabetes Rac1 transcriptional activation in the retina is mediated by acetylation of NF-kB, and modulation of acetylation during the early stages of diabetic retinopathy has potential to inhibit/retard its development.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
Proteína de Unión al GTP rac1
/
Retinopatía Diabética
Límite:
Animals
Idioma:
En
Revista:
Exp Eye Res
Año:
2016
Tipo del documento:
Article