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Inhibition of neddylation by MLN4924 improves neointimal hyperplasia and promotes apoptosis of vascular smooth muscle cells through p53 and p62

文献类型：期刊论文

作者Ai, Tang-Jun1,2,5,6,7; Sun, Jian-Yong1,2,6,7; Du, Lin-Juan1,2,5,6,7; Shi, Chaoji1,2,6,7; Li, Chao1,2,5,6,7; Sun, Xue-Nan1,2,5,6,7; Liu, Yan1,2,6,7; Duan, Sheng-Zhong1,2,6,7; Li, Lihui4; Jia, Lijun4
刊名CELL DEATH AND DIFFERENTIATION
出版日期2018
卷号25期号:2页码:319-329
关键词HSP90 beta lipid metabolism corylin SREBPs proteasomal degradation
ISSN号1350-9047
DOI10.1038/cdd.2017.160
文献子类Article
英文摘要Targeting apoptosis of vascular smooth muscle cells (VSMCs) represents an attractive approach to diminish the occurrence of restenosis. Neddylation is a highly conserved post-translational modification process and inhibition of neddylation has been shown to regulate apoptosis of other cells. However, the impacts of neddylation inhibition on VSMCs and neointimal hyperplasia have not been studied. In our present study, we have shown that MLN4924, a selective inhibitor of NEDD8-activating enzyme (NAE), markedly inhibited neointimal hyperplasia and accumulation of VSMCs, whereas increased apoptosis in the vascular wall. In vitro studies revealed that MLN4924 induced G2/M arrest and apoptosis of human VSMCs. Knockdown of NAE1 had similar effects. MLN4924 upregulated p53 and p62 in human VSMCs. Knockdown of either p53 or p62 mitigated the impacts of MLN4924 on G2/M arrest and apoptosis. Moreover, p53 knockdown abolished MLN4924-induced upregulation of p62. Finally, smooth muscle p53 knockout mice were generated and subjected to femoral artery injury and MLN4924 treatment. Deficiency of p53 in smooth muscle blocked the effects of MLN4924 on neointimal hyperplasia and apoptosis. Together, our results revealed that neddylation inhibition induces apoptosis through p53 and p62 in VSMCs and improves neointimal hyperplasia mainly by promoting apoptosis through smooth muscle p53 in mice. These pre-clinical data provide strong translational implications for targeting restenosis by perturbation of neddylation using MLN4924.
学科主题Biochemistry & Molecular Biology ; Cell Biology
WOS关键词PERCUTANEOUS CORONARY INTERVENTION ; DRUG-ELUTING STENTS ; DNA-DAMAGE ; NEDD8-ACTIVATING ENZYME ; CANCER-CELLS ; CHECKPOINT ACTIVATION ; PROTEIN NEDDYLATION ; GENE-TRANSFER ; RESTENOSIS ; AUTOPHAGY
语种英语
WOS记录号WOS:000424342100008
出版者NATURE PUBLISHING GROUP
版本出版稿
源URL[http://202.127.25.144/handle/331004/686]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Stomatol, Shanghai 200011, Peoples R China;
2.Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Sch Stomatol,Lab Oral Microbiota & Syst Dis, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China;
3.Huazhong Univ Sci & Technol, Minist Educ, Key Lab Mol Biophys, Cellular Signaling Lab, Wuhan 430074, Hubei, Peoples R China,
4.Shanghai Univ Tradit Chinese Med, Longhua Hosp, Canc Inst, Shanghai 200032, Peoples R China;
5.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China;
6.Shanghai Jiao Tong Univ, Sch Med, Natl Clin Res Ctr Stomatol, Shanghai 200011, Peoples R China;
7.Shanghai Jiao Tong Univ, Sch Med, Shanghai Res Inst Stomatol, Shanghai 200011, Peoples R China;
推荐引用方式
GB/T 7714		 Ai, Tang-Jun,Sun, Jian-Yong,Du, Lin-Juan,et al. Inhibition of neddylation by MLN4924 improves neointimal hyperplasia and promotes apoptosis of vascular smooth muscle cells through p53 and p62[J]. CELL DEATH AND DIFFERENTIATION,2018,25(2):319-329.
APA Ai, Tang-Jun.,Sun, Jian-Yong.,Du, Lin-Juan.,Shi, Chaoji.,Li, Chao.,...&,.(2018).Inhibition of neddylation by MLN4924 improves neointimal hyperplasia and promotes apoptosis of vascular smooth muscle cells through p53 and p62.CELL DEATH AND DIFFERENTIATION,25(2),319-329.
MLA Ai, Tang-Jun,et al."Inhibition of neddylation by MLN4924 improves neointimal hyperplasia and promotes apoptosis of vascular smooth muscle cells through p53 and p62".CELL DEATH AND DIFFERENTIATION 25.2(2018):319-329.

入库方式： OAI收割

来源：上海营养与健康研究所

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