title: Helix B surface peptide administered after insult of ischemia reperfusion improved renal function, structure and apoptosis through beta common receptor/erythropoietin receptor and PI3K/Akt pathway in a murine model.
abstract: Erythropoietin (EPO) has been well recognized as a tissue protective agent by inhibiting apoptosis and inflammation. The tissue protective effect of EPO, however, only occurs at a high dosage, which may elicit severe side-effects at the meantime. Helix B surface peptide (HBSP), a novel peptide derived from the non-erythropoietic helix B of EPO, plays a specific role in tissue protection. We investigated effects of HBSP and the expression of its heterodimeric receptor, beta common receptor (βcR)/EPO receptor ( ), in a murine renal ischemia reperfusion (IR) injury model. HBSP significantly ameliorated renal dysfunction and tissue damage, decreased apoptotic cells in the kidney and reduced activation of caspase-9 and -3. The βcR/EPOR in the kidney was up-regulated by IR, but down-regulated by HBSP. Further investigation revealed that the expression and phosphorylation of Akt was dramatically enhanced by HBSP, but strongly reversed by wortmannin, the PI3K inhibitor. Wortmannin intervention improved βcR/EPOR expression, promoted caspase-9 and -3 activation, and increased active caspase-3 positive cells, while renal function and structure, and apoptotic cell counts scarcely changed. This result indicates a significant contribution of PI3K/Akt signaling pathway in the renoprotection of HBSP. The therapeutic effects of HBSP in this study suggest that HBSP could be a better candidate for renal protection.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, P R China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.forename: Tian
authors.initials: T
authors.lastname: Zhao
authors.forename: Miao
authors.initials: M
authors.lastname: Lin
authors.forename: Zitong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Linkun
authors.initials: L
authors.lastname: Hu
authors.forename: Yichen
authors.initials: Y
authors.lastname: Jia
authors.forename: Yinjia
authors.initials: Y
authors.lastname: Xue
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Qunye
authors.initials: Q
authors.lastname: Tang
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Ruiming
authors.initials: R
authors.lastname: Rong
authors.forename: Tongyu
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D004921:Erythropoietin / Q000008:administration & dosage* / Q000235:genetics; D007511:Ischemia / Q000150:complications; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy*; D015398:Signal Transduction
chemical_list: D010455:Peptides; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt