A novel proteolysis-resistant cyclic helix B peptide ameliorates kidney ischemia reperfusion injury
文献类型：期刊论文
| 作者 | Yang, Cheng2,5; Xu, Zhongliang4; Zhao, Zitong2,5; Li, Long2,5; Zhao, Tian2,5; Peng, Dian4; Xu, Ming2,5; Rong, Ruiming1,2,5; Long, Ya-Qiu4; Zhu, Tongyu2,3,5 |
| 刊名 | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
 |
| 出版日期 | 2014-11 |
| 卷号 | 1842期号:11页码:2306-2317 |
| 关键词 | Cyclic helix B peptide Metabolic stability Kidney ischemia reperfusion injury Autophagy Apoptosis Inflammation |
| ISSN号 | 0925-4439 |
| DOI | 10.1016/j.bbadis.2014.09.001 |
| 文献子类 | Article |
| 英文摘要 | Helix B surface peptide (HBSP), derived from erythropoietin, displays powerful tissue protection during kidney ischemia reperfusion (IR) injury without erythropoietic side effects. We employed cyclization strategy for the first time, and synthesized thioether-cyclized helix B peptide (CHBP) to improve metabolic stability and renoprotective effect. LC-MS/MS analysis was adopted to examine the stability of CHBP in vitro and in vivo. The renoprotective effect of CHBP in terms of renal function, apoptosis, inflammation, extracellular matrix deposition, and histological injury was also detected in vivo and in vitro. Antibody array and western blot were performed to analyze the signal pathway of involvement by CHBP in the IR model and renal tubular epithelial cells. In this study, thioether-cyclized peptide was significantly stable in vivo and in vitro. One dose of 8 nmol/kg CHBP administered intraperitoneally at the onset of reperfusion improved renal protection compared with three doses of 8 nmol/kg linear HBSP in a 48 h murine IR model. In a one-week model, the one dose CHBP-treated group exhibited remarkably improved renal function over the IR group, and attenuated kidney injury, including reduced inflammation and apoptosis. Interestingly, we found that the phosphorylation of autophagy protein mTORC1 was dramatically reduced upon CHBP treatment. We also demonstrated that CHBP induced autophagy via inhibition of mTORC1 and activation of mTORC2, leading to renoprotective effects on IR. Our results indicate that the novel metabolically stable CHBP is a promising therapeutic medicine for kidney IR injury treatment. (C) 2014 Elsevier B.V. All rights reserved. |
| WOS关键词 | RENAL ISCHEMIA/REPERFUSION INJURY ; TERTIARY STRUCTURE ; GRB2-SH2 DOMAIN ; CELL-DEATH ; AUTOPHAGY ; ERYTHROPOIETIN ; APOPTOSIS ; RECEPTOR ; PROTECTS ; PATHWAY |
| 资助项目 | National Natural Science Foundation of China[81270832] ; National Natural Science Foundation of China[81270833] ; National Natural Science Foundation of China[81021062] ; National Natural Science Foundation of China[81370852] ; National Natural Science Foundation of China[81123004] ; National Natural Science Foundation of China[81400752] ; National Natural Science Foundation of China[21302201] ; Science and Technology Commission of Shanghai Municipality[12ZR1405500] ; Science and Technology Commission of Shanghai Municipality[13ZR1447700] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000343844800026 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276857]  |
| 专题 | 药物化学研究室 |
| 通讯作者 | Rong, Ruiming |
| 作者单位 | 1.Fudan Univ, Zhongshan Hosp, Dept Transfus, Shanghai 200433, Peoples R China; 2.Shanghai Key Lab Organ Transplantat, Shanghai, Peoples R China; 3.Fudan Univ, Zhongshan Hosp, Qingpu Branch, Shanghai 200032, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 200031, Peoples R China; 5.Fudan Univ, Zhongshan Hosp, Dept Urol, Shanghai 200032, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Yang, Cheng,Xu, Zhongliang,Zhao, Zitong,et al. A novel proteolysis-resistant cyclic helix B peptide ameliorates kidney ischemia reperfusion injury[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,2014,1842(11):2306-2317. |
| APA | Yang, Cheng.,Xu, Zhongliang.,Zhao, Zitong.,Li, Long.,Zhao, Tian.,...&Zhu, Tongyu.(2014).A novel proteolysis-resistant cyclic helix B peptide ameliorates kidney ischemia reperfusion injury.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,1842(11),2306-2317. |
| MLA | Yang, Cheng,et al."A novel proteolysis-resistant cyclic helix B peptide ameliorates kidney ischemia reperfusion injury".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 1842.11(2014):2306-2317. |
入库方式： OAI收割
来源：上海药物研究所
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