Dynamin-related protein inhibitor downregulates reactive oxygen species levels to indirectly suppress high glucose-induced hyperproliferation of vascular smooth muscle cells
| Autor: | Yong Li, Xiaofei Jiang, Xinyu Zhuang, Alimujiang Maimaitijiang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Dynamins
0301 basic medicine Vascular smooth muscle Biophysics MFN2 Down-Regulation Biology Mitochondrial Dynamics Biochemistry Muscle Smooth Vascular Pathogenesis 03 medical and health sciences Downregulation and upregulation Protein biosynthesis Animals Molecular Biology Cells Cultured Cell Proliferation Quinazolinones Dynamin chemistry.chemical_classification Reactive oxygen species Cell Biology Rats Cell biology Oxidative Stress Glucose 030104 developmental biology chemistry Mitochondrial fission Reactive Oxygen Species |
| Zdroj: | Biochemical and Biophysical Research Communications. 471:474-478 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2016.02.051 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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