Sodium Tanshinone IIA Silate Inhibits High Glucose-Induced Vascular Smooth Muscle Cell Proliferation and Migration through Activation of AMP-Activated Protein Kinase | |
Wu, Wen-yu1,2; Yan, Hong2; Wang, Xin-bo2; Gui, Yu-zhou2; Gao, Fei2; Tang, Xi-lan1; Qin, Yin-lin3; Su, Mei3; Chen, Tao3; Wang, Yi-ping2![]() | |
刊名 | PLOS ONE
![]() |
2014-04-16 | |
卷号 | 9期号:4 |
ISSN号 | 1932-6203 |
DOI | 10.1371/journal.pone.0094957 |
文献子类 | Article |
英文摘要 | The proliferation of vascular smooth muscle cells may perform a crucial role in the pathogenesis of diabetic vascular disease. AMPK additionally exerts several salutary effects on vascular function and improves vascular abnormalities. The current study sought to determine whether sodium tanshinone IIA silate (STS) has an inhibitory effect on vascular smooth muscle cell (VSMC) proliferation and migration under high glucose conditions mimicking diabetes without dyslipidemia, and establish the underlying mechanism. In this study, STS promoted the phosphorylation of AMP-activated protein kinase (AMPK) at T172 in VSMCs. VSMC proliferation was enhanced under high glucose (25 mM glucose, HG) versus normal glucose conditions (5.5 mM glucose, NG), and this increase was inhibited significantly by STS treatment. We utilized western blotting analysis to evaluate the effects of STS on cell-cycle regulatory proteins and found that STS increased the expression of p53 and the Cdk inhibitor, p21, subsequent decreased the expression of cell cycle-associated protein, cyclin D1. We further observed that STS arrested cell cycle progression at the G(0)/G(1) phase. Additionally, expression and enzymatic activity of MMP-2, translocation of NF-kappa B, as well as VSMC migration were suppressed in the presence of STS. Notably, Compound C (CC), a specific inhibitor of AMPK, as well as AMPK siRNA blocked STS-mediated inhibition of VSMC proliferation and migration. We further evaluated its potential for activating AMPK in aortas in animal models of type 2 diabetes and found that Oral administration of STS for 10 days resulted in activation of AMPK in aortas from ob/ob or db/db mice. In conclusion, STS inhibits high glucose-induced VSMC proliferation and migration, possibly through AMPK activation. The growth suppression effect may be attributable to activation of AMPK-p53-p21 signaling, and the inhibitory effect on migration to the AMPK/NF-kappa B signaling axis. |
资助项目 | Shanghai Committee of Science and Technology, China[13DZ2290200] ; National Basic Research Program of China[2009CB930300] ; Carefree Pharmaceutical Co., Ltd[00000000] |
WOS关键词 | NF-KAPPA-B ; TRANSCRIPTION FACTOR ; ATHEROSCLEROSIS ; EXPRESSION ; PATHWAY ; GROWTH ; ACID ; RATS ; P53 ; TARGET |
WOS研究方向 | Science & Technology - Other Topics |
语种 | 英语 |
出版者 | PUBLIC LIBRARY SCIENCE |
WOS记录号 | WOS:000336863900087 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/277112] ![]() |
专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
通讯作者 | Wang, Yi-ping |
作者单位 | 1.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China; 3.Carefree Pharmaceut Co Ltd, Nanjing, Jiangsu, Peoples R China |
推荐引用方式 GB/T 7714 | Wu, Wen-yu,Yan, Hong,Wang, Xin-bo,et al. Sodium Tanshinone IIA Silate Inhibits High Glucose-Induced Vascular Smooth Muscle Cell Proliferation and Migration through Activation of AMP-Activated Protein Kinase[J]. PLOS ONE,2014,9(4). |
APA | Wu, Wen-yu.,Yan, Hong.,Wang, Xin-bo.,Gui, Yu-zhou.,Gao, Fei.,...&Wang, Yi-ping.(2014).Sodium Tanshinone IIA Silate Inhibits High Glucose-Induced Vascular Smooth Muscle Cell Proliferation and Migration through Activation of AMP-Activated Protein Kinase.PLOS ONE,9(4). |
MLA | Wu, Wen-yu,et al."Sodium Tanshinone IIA Silate Inhibits High Glucose-Induced Vascular Smooth Muscle Cell Proliferation and Migration through Activation of AMP-Activated Protein Kinase".PLOS ONE 9.4(2014). |
个性服务 |
查看访问统计 |
相关权益政策 |
暂无数据 |
收藏/分享 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论