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

Exp Biol Med (Maywood). 2013 Jan;238(1):111-9. doi: 10.1258/ebm.2012.012185.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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