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: Cheng Yang, Tian Zhao, Miao Lin, Zitong Zhao, Linkun Hu, Yichen Jia, Yinjia Xue, Ming Xu, Qunye Tang, Bin Yang, Ruiming Rong, Tongyu Zhu
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 238 Issue 1 Pg. 111-9 (Jan 2013) ISSN: 1535-3699 [Electronic] England
• PMID: 23479770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides
• Receptors, Erythropoietin
• Erythropoietin
• Phosphatidylinositol 3-Kinases
• Oncogene Protein v-akt

Topics

• Animals
• Apoptosis
• Erythropoietin (administration & dosage, genetics)
• Ischemia (complications)
• Kidney (pathology, physiopathology)
• Male
• Mice
• Mice, Inbred BALB C
• Oncogene Protein v-akt (metabolism)
• Peptides (administration & dosage, genetics)
• Phosphatidylinositol 3-Kinases (metabolism)
• Receptors, Erythropoietin (metabolism)
• Reperfusion Injury (drug therapy)
• Signal Transduction