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

• Published in: BMC neuroscience Vol. 8; no. 1; p. 81
• Main Authors: Hong, Samin, Lee, Jong Eun, Kim, Chan Yun, Seong, Gong Je
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.10.2007; BioMed Central; BMC
• Subjects: Agmatine - pharmacology; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Arginine; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Hypoxia - drug effects; Cell Hypoxia - physiology; Cell Line, Transformed; Cell Survival - drug effects; Cell Survival - physiology; Comparative analysis; Ganglion; Guanidine; Health aspects; Humans; Neurons; Neuroprotective Agents - pharmacology; Polyamines; Protein kinases; Proteins; Rats; Rats, Sprague-Dawley; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - pathology; Retinal Ganglion Cells - physiology; South Korea
• ISSN: 1471-2202; 1471-2202
• DOI: 10.1186/1471-2202-8-81

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. 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. 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.