Dynamin-related protein inhibitor downregulates reactive oxygen species levels to indirectly suppress high glucose-induced hyperproliferation of vascular smooth muscle cells.
Biochem Biophys Res Commun
; 471(4): 474-8, 2016 Mar 18.
Article
en En
| MEDLINE
| ID: mdl-26903301
ABSTRACT
Hyperproliferation of vascular smooth muscle cells is a pathogenic mechanism common in diabetic vascular complications and is a putatively important therapeutic target. This study investigated multiple levels of biology, including cellular and organellar changes, as well as perturbations in protein synthesis and morphology. Quantitative and qualitative analysis was utilized to assess the effect of mitochondrial dynamic changes and reactive oxygen species(ROS) levels on high-glucose-induced hyperproliferation of vascular smooth muscle cells. The data demonstrated that the mitochondrial fission inhibitor Mdivi-1 and downregulation of ROS levels both effectively inhibited the high-glucose-induced hyperproliferation of vascular smooth muscle cells. Downregulation of ROS levels played a more direct role and ROS levels were also regulated by mitochondrial dynamics. Increased ROS levels induced excessive mitochondrial fission through dynamin-related protein (Drp 1), while Mdivi-1 suppressed the sensitivity of Drp1 to ROS levels, thus inhibiting excessive mitochondrial fission under high-glucose conditions. This study is the first to propose that mitochondrial dynamic changes and ROS levels interact with each other and regulate high-glucose-induced hyperproliferation of vascular smooth muscle cells. This finding provides novel ideas in understanding the pathogenesis of diabetic vascular remodeling and intervention.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Especies Reactivas de Oxígeno
/
Dinaminas
/
Quinazolinonas
/
Glucosa
/
Músculo Liso Vascular
Tipo de estudio:
Qualitative_research
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2016
Tipo del documento:
Article