SIRT3 deficiency increases mitochondrial oxidative stress and promotes migration of retinal pigment epithelial cells.
Exp Biol Med (Maywood)
; 246(8): 877-887, 2021 04.
Article
en En
| MEDLINE
| ID: mdl-33423553
ABSTRACT
Retinal pigment epithelial cells are closely associated with the pathogenesis of diabetic retinopathy. The mechanism by which diabetes impacts retinal pigment epithelial cell function is of significant interest. Sirtuins are an important class of proteins that primarily possess nicotinamide adenine dinucleotide-dependent deacetylases activity and involved in various cellular physiological and pathological processes. Here, we aimed to examine the role of sirtuins in the induction of diabetes-associated retinal pigment epithelial cell dysfunction. High glucose and platelet-derived growth factor (PDGF) treatment induced epithelial-mesenchymal transition and the migration of retinal pigment epithelial cells, and decreased sirtuin-3 expression. Sirtuin-3 knockdown using siRNA increased epithelial-mesenchymal transition and migration of retinal pigment epithelial cells. In contrast, sirtuin-3 overexpression attenuated the effects caused by high glucose and PDGF on epithelial-mesenchymal transition and migration of retinal pigment epithelial cells, suggesting that sirtuin-3 deficiency contributed to retinal pigment epithelial cell dysfunction induced by high glucose and PDGF. Mechanistically, sirtuin-3 deficiency induced retinal pigment epithelial cell dysfunction by the overproduction of mitochondrial reactive oxygen species. These results suggest that sirtuin-3 deficiency mediates the migration of retinal pigment epithelial cells, at least partially by increasing mitochondrial oxidative stress, and shed light on the importance of sirtuin-3 and mitochondrial reactive oxygen species as potential targets in diabetic retinopathy therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Movimiento Celular
/
Estrés Oxidativo
/
Retinopatía Diabética
/
Células Epiteliales
/
Epitelio Pigmentado de la Retina
/
Sirtuina 3
/
Mitocondrias
Límite:
Humans
Idioma:
En
Revista:
Exp Biol Med (Maywood)
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
/
MEDICINA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China