Molecular Medicine

, Volume 17, Issue 9–10, pp 883–892 | Cite as

A Nonerythropoietic Peptide that Mimics the 3D Structure of Erythropoietin Reduces Organ Injury/Dysfunction and Inflammation in Experimental Hemorrhagic Shock

  • Nimesh S. A. Patel
  • Kiran K. Nandra
  • Michael Brines
  • Massimo Collino
  • W. S. Fred Wong
  • Amar Kapoor
  • Elisa Benetti
  • Fera Y. Goh
  • Roberto Fantozzi
  • Anthony Cerami
  • Christoph Thiemermann
Research Article


Recent studies have shown that erythropoietin, critical for the differentiation and survival of erythrocytes, has cytoprotective effects in a wide variety of tissues, including the kidney and lung. However, erythropoietin has been shown to have a serious side effect—an increase in thrombovascular effects. We investigated whether pyroglutamate helix B-surface peptide (pHBSP), a nonerythropoietic tissue-protective peptide mimicking the 3D structure of erythropoietin, protects against the organ injury/dysfunction and inflammation in rats subjected to severe hemorrhagic shock (HS). Mean arterial blood pressure was reduced to 35 ± 5 mmHg for 90 min followed by resuscitation with 20 mL/kg Ringer Lactate for 10 min and 50% of the shed blood for 50 min. Rats were euthanized 4 h after the onset of resuscitation. pHBSP was administered 30 min or 60 min into resuscitation. HS resulted in significant organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung). In rats subjected to HS, pHBSP significantly attenuated (i) organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung), (ii) increased the phosphorylation of Akt, glycogen synthase kinase-3β and endothelial nitric oxide synthase, (iii) attenuated the activation of nuclear factor (nf)-κB and (iv) attenuated the increase in p38 and extracellular signal-regulated kinase (ERK)1/2 phosphorylation. pHBSP protects against multiple organ injury/dysfunction and inflammation caused by severe hemorrhagic shock by a mechanism that may involve activation of Akt and endothelial nitric oxide synthase, and inhibition of glycogen synthase kinase-3β and NF-κB.



NSAP is supported by a Kidney Research United Kingdom Post-Doctoral Fellowship (PDF4/2009). KKN is supported by a British Heart Foundation PhD Studentship (FS/10/57/28485). WSFW is supported, in part, by a Bio-Medical Research Council of Singapore Grant (09/1/21/19/595). This work is supported, in part, by the William Harvey Research Foundation. This work forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit which is supported and funded by the National Institute of Health Research.


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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Nimesh S. A. Patel
    • 1
  • Kiran K. Nandra
    • 1
  • Michael Brines
    • 2
  • Massimo Collino
    • 3
  • W. S. Fred Wong
    • 4
  • Amar Kapoor
    • 1
  • Elisa Benetti
    • 3
  • Fera Y. Goh
    • 4
  • Roberto Fantozzi
    • 3
  • Anthony Cerami
    • 2
  • Christoph Thiemermann
    • 1
  1. 1.Barts and The London School of Medicine & Dentistry, William Harvey Research Institute, Centre for Translational Medicine and TherapeuticsQueen Mary University of LondonLondonUK
  2. 2.Araim PharmaceuticalsOssiningUSA
  3. 3.Department of Anatomy, Pharmacology and Forensic MedicineUniversity of TurinTurinItaly
  4. 4.Department of Pharmacology and Immunology ProgramNational University Health System, National University of SingaporeSingaporeSingapore

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