A novel proteolysis-resistant cyclic helix B peptide ameliorates kidney ischemia reperfusion injury

doi:10.1016/j.bbadis.2014.09.001

	A novel proteolysis-resistant cyclic helix B peptide ameliorates kidney ischemia reperfusion injury
	Yang, Cheng 2,5; Xu, Zhongliang 4; Zhao, Zitong 2,5; Li, Long 2,5; Zhao, Tian 2,5; Peng, Dian 4; Xu, Ming 2,5; Rong, Ruiming 1,2,5; Long, Ya-Qiu 4; Zhu, Tongyu 2,3,5
刊名	BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
	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.
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关键词	RENAL ISCHEMIA/REPERFUSION INJURY ; TERTIARY STRUCTURE ; GRB2-SH2 DOMAIN ; CELL-DEATH ; AUTOPHAGY ; ERYTHROPOIETIN ; APOPTOSIS ; RECEPTOR ; PROTECTS ; PATHWAY
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000343844800026
内容类型	期刊论文
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.