Prothymosin-alpha plays a defensive role in retinal ischemia through necrosis and apoptosis inhibition

Cell Death Differ. 2009 Feb;16(2):349-58. doi: 10.1038/cdd.2008.159. Epub 2008 Nov 7.

Abstract

Prothymosin-alpha (ProTalpha) causes a switch in cell death mode from necrosis to neurotrophin-reversible apoptosis in primary cultured cortical neurons. In the present study, post-ischemic administration (3 or 24 h, intravenously) of recombinant mouse ProTalpha without neurotrophins completely prevented ischemia-induced retinal damage accompanying necrosis and apoptosis, as well as dysfunction assessed by electroretinogram. Treatments with anti-erythropoietin (EPO) or brain-derived neurotrophic factor (BDNF) immunoglobulin G (IgG) reversed ProTalpha-induced inhibition of apoptosis. ProTalpha upregulated retinal EPO and BDNF levels in the presence of ischemia. Moreover, intravitreous administration of anti-ProTalpha IgG or an antisense oligodeoxynucleotide for ProTalpha accelerated ischemia-induced retinal damage. We also observed that ischemia treatment caused a depletion of ProTalpha from retinal cells. Altogether, these results suggest that the systemic administration of ProTalpha switches ischemia-induced necrosis to apoptosis, which in turn is inhibited by neurotrophic factors upregulated by ProTalpha and ischemia. ProTalpha released upon ischemic stress was found to have a defensive role in retinal ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Antibodies / pharmacology
  • Apoptosis*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Erythropoietin / metabolism
  • Ischemia / pathology*
  • Male
  • Mice
  • Necrosis*
  • Protein Precursors / physiology*
  • Reperfusion Injury / prevention & control
  • Retina / metabolism
  • Retinal Vessels / pathology*
  • Thymosin / analogs & derivatives*
  • Thymosin / physiology

Substances

  • Antibodies
  • Brain-Derived Neurotrophic Factor
  • Protein Precursors
  • prothymosin alpha
  • Erythropoietin
  • Thymosin