Effect of hypothalamic proline-rich peptide (PRP-1) on neuronal and bone marrow cell apoptosis

Neurochem Res. 2007 Nov;32(11):1898-905. doi: 10.1007/s11064-007-9379-9. Epub 2007 Jun 5.

Abstract

The AGAPEPAEPAQPGVY proline-rich peptide (PRP-1) was isolated from neurosecretory granules of the bovine neurohypophysis; it is produced by N. supraopticus and N. paraventricularis. It has been shown that PRP-1 has many potentially beneficial biological effects including immunoregulatory, hematopoietic, antimicrobial and anti-neurodegenerative properties. Here we investigated the influence of PRP-1 on staurosporine-induced apoptosis of postnatal hippocampal cells and on doxorubicin-induced bone marrow granulocyte- and monocyte apoptosis. The intention was to further characterize the effect of PRP-1 on the survival rate of neurons and in context with myelopoiesis. We demonstrate that PRP-1 significantly reduced apoptosis of postnatal hippocampal cells induced by staurosporine. The protective effect of PRP-1 against apoptotic cell death was shown to be both time- and dose-dependent. Neuroprotection was more pronounced after prolonged pretreatment of the cells with PRP-1 before the induction of apoptosis with staurosporine. The related peptide [arg(8)]vasopressin did not reveal neuroprotection. PRP-1 also significantly reduced apoptosis of bone marrow monocytes and granulocytes induced by doxorubicin. This protective effect lasted for 2-4 h and was not detectable anymore after 24 h when PRP-1 and doxorubicin were added simultaneously. Previously obtained data and results of the current studies suggested that the hypothalamic PRP-1 possibly represents an endogenous peptide whose primary functions are to regulate myelopoiesis and neuron survival as we provide evidence that PRP can differentially reduce both staurosporine- and doxorubicin-induced hippocampal and bone marrow cell apoptosis.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Bone Marrow Cells / drug effects*
  • Doxorubicin / pharmacology
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Neurons / cytology*
  • Neurons / drug effects
  • Peptides / pharmacology*
  • Proline-Rich Protein Domains
  • Rats
  • Staurosporine / antagonists & inhibitors
  • Staurosporine / pharmacology

Substances

  • Peptides
  • Doxorubicin
  • Staurosporine