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S. Hong, J. Lee, S.-H. Han, G. Seong; Agmatine Protects Retinal Ganglion Cells From Hypoxia-Induced Apoptosis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4372.
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To investigate the neuroprotective effect and cellular mechanism of agmatine on the hypoxia-induced apoptosis of retinal ganglion cells (RGCs).
Transformed rat RGCs (RGC-5) were cultured in a closed hypoxic chamber, in which oxygen level was controlled to 5% normal partial pressure (5% O2, 5% CO2, 90% N2). With or without agmatine, cell viability was determined by lactate dehydrogenase (LDH) assay and apoptosis was established by annexin-V and caspase-3 assays. The expression and activity of mitogen-activated protein kinases (MAPKs; JNK, ERK p44/42, and p38) and nuclear factor-kappa B (NF-kB) were investigated by Western immunoblot analysis. The effect of agmatine was compared with brain-derived neurotrophic factor (BDNF), a well-known protective neurotrophin to RGCs.
After 48 hours of hypoxic culture, 52.3% cell loss was evident and it was reduced to 25.6% when agmatine was present, as demonstrated by LDH assay. When BDNF was present, the cell death was reduced to 30.1%. This cell loss was due to apoptotic cell death, as established by annexin-V and caspase-3 assays. Hypoxic injury induced the phosphorylated MAPKs and NF-kB, and agmatine suppressed the phosphorylated JNK and NF-kB but not ERK and p38. BDNF suppressed the phosphorylated ERK and p38 but not JNK and NF-kB.
These results showed that agmatine has a neuroprotective effect against hypoxia-induced RGC damage, and its effect is more powerful than BDNF. This protection of agmatine is associated with JNK and NF-kB pathways, and it has a different working mechanism with BDNF. Our data suggest that agmatine may lead to a novel therapeutic strategy to reduce RGC injury related hypoxia.
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