Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line

BMC Neurosci. 2007 Oct 2:8:81. doi: 10.1186/1471-2202-8-81.

Abstract

Background: Agmatine is an endogenous polyamine formed by the decarboxylation of L-arginine. We investigated the protective effects of agmatine against hypoxia-induced apoptosis of immortalized rat retinal ganglion cells (RGC-5). RGC-5 cells were cultured in a closed hypoxic chamber (5% O2) with or without agmatine. Cell viability was determined by lactate dehydrogenase (LDH) assay and apoptosis was examined by annexin V and caspase-3 assays. Expression and phosphorylation of mitogen-activated protein kinases (MAPKs; JNK, ERK p44/42, and p38) and nuclear factor-kappa B (NF-kappaB) were investigated by Western immunoblot analysis. The effects of agmatine were compared to those of brain-derived neurotrophic factor (BDNF), a well-known protective neurotrophin for retinal ganglion cells.

Results: After 48 hours of hypoxic culture, the LDH assay showed 52.3% cell loss, which was reduced to 25.6% and 30.1% when agmatine and BDNF were administered, respectively. This observed cell loss was due to apoptotic cell death, as established by annexin V and caspase-3 assays. Although total expression of MAPKs and NF-kappaB was not influenced by hypoxic injury, phosphorylation of these two proteins was increased. Agmatine reduced phosphorylation of JNK and NF-kappaB, while BDNF suppressed phosphorylation of ERK and p38.

Conclusion: Our results show that agmatine has neuroprotective effects against hypoxia-induced retinal ganglion cell damage in RGC-5 cells and that its effects may act through the JNK and NF-kappaB signaling pathways. Our data suggest that agmatine may lead to a novel therapeutic strategy to reduce retinal ganglion cell injury related to hypoxia.

Publication types

  • Comparative Study
  • Retracted Publication

MeSH terms

  • Agmatine / pharmacology*
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology
  • Cell Line, Transformed
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Humans
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / pathology
  • Retinal Ganglion Cells / physiology

Substances

  • Neuroprotective Agents
  • Agmatine