Ginsenoside Rg1 Protects against Oxidative Stress-induced Neuronal Apoptosis through Myosin IIA-actin Related Cytoskeletal Reorganization
Autor: | Qian Liu, Jingrong Wang, Zhengyu Cao, Boyang Yu, Yisha Tan, Yuanyuan Zhang, Guosheng Cao, Yanni Lv, Xiaonan Ma, Nan Jiang, Yan Wang, Junping Kou, Yingqiong Xu |
---|---|
Rok vydání: | 2016 |
Předmět: |
neuronal apoptosis
0301 basic medicine myosin IIA-actin interaction Myosin light-chain kinase Ginsenosides Cell Survival Fluorescent Antibody Technique Apoptosis macromolecular substances Biology medicine.disease_cause PC12 Cells Applied Microbiology and Biotechnology Neuroprotection Rats Sprague-Dawley 03 medical and health sciences Microscopy Electron Transmission Myosin medicine Animals Immunoprecipitation Cytoskeleton Molecular Biology Cells Cultured Ecology Evolution Behavior and Systematics Actin Ginsenoside Rg1 Caspase 3 Nonmuscle Myosin Type IIA cytoskeleton Hydrogen Peroxide Cell Biology Flow Cytometry Rats Cell biology Oxidative Stress 030104 developmental biology Signal transduction Reactive Oxygen Species Oxidative stress Research Paper Developmental Biology |
Zdroj: | International Journal of Biological Sciences |
ISSN: | 1449-2288 |
Popis: | Oxidative stress-induced cytoskeletal dysfunction of neurons has been implicated as a crucial cause of cell apoptosis or death in the central nervous system (CNS) diseases, such as neurodegenerative and psychiatric diseases. The application of neuroprotectants rescuing the neurons from cytoskeletal damage and apoptosis can be a potential treatment for these CNS diseases. Ginsenoside Rg1 (Rg1), one of the major active components of ginseng, has been reported possessing notable neuroprotective activities. However, there is rare report about its effect on cytoskeleton and its undergoing mechanism. The current study is to reveal the regulatory effects of Rg1 on cytoskeletal and morphological lesion in oxidative stress-induced neuronal apoptosis. The results demonstrated that pre-treatment with Rg1 (0.1-10 μM) attenuated hydrogen peroxide (H2O2)-induced neuronal apoptosis and oxidative stress through reducing the intracellular reactive oxygen species (ROS) production and methane dicarboxylic aldehyde (MDA) level. The Rg1 treatment also abolished H2O2-induced morphological changes, including cell rounding, membrane blebbing, neurite retraction and nuclei condensation, which were generated by myosin IIA-actin interaction. These effects were mediated via the down-regulation of caspase-3, ROCK1 (Rho-associated kinase1) activation and myosin light chain (MLC, Ser-19) phosphorylation. Furthermore, inhibiting myosin II activity with blebbistatin partly blocked the neuroprotective effects of Rg1. The computer-aided homology modelling revealed that Rg1 preferentially positioned in the actin binding cleft of myosin IIA and might block the binding of myosin IIA to actin filaments. Accordingly, the neuroprotective mechanism of Rg1 is related to the activity that inhibits myosin IIA-actin interaction and the caspase-3/ROCK1/MLC signaling pathway. These findings put some insights into the unique neuroprotective properties of Rg1 associated with the regulation of myosin IIA-actin cytoskeletal structure under oxidative stress and provide experimental evidence for Rg1 in CNS diseases. |
Databáze: | OpenAIRE |
Externí odkaz: |