Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Braz J Med Biol Res. 2010 Apr;43(4):356-8. doi: 10.1590/S0100-879X2010007500018. Epub 2010 Mar 19.
Agmatine has neuroprotective effects on retinal ganglion cells (RGCs) as well as cortical and spinal neurons. It protects RGCs from oxidative stress even when it is not present at the time of injury. As agmatine has high affinity for various cellular receptors, we assessed protective mechanisms of agmatine using transformed RGCs (RGC-5 cell line). Differentiated RGC-5 cells were pretreated with 100 muM agmatine and consecutively exposed to 1.0 mM hydrogen peroxide (H2O2). Cell viability was determined by measuring lactate dehydrogenase (LDH), and the effects of selective alpha 2-adrenergic receptor antagonist yohimbine (0-500 nM) and N-methyl-D-aspartic acid (NMDA) receptor agonist NMDA (0-100 microM) were evaluated. Agmatine's protective effect was compared to a selective NMDA receptor antagonist MK-801. After a 16-h exposure to H2O2, the LDH assay showed cell loss greater than 50%, which was reduced to about 30% when agmatine was pretreated before injury. Yohimbine almost completely inhibited agmatine's protective effect, but NMDA did not. In addition, MK-801 (0-100 microM) did not significantly attenuate the H2O2-induced cytotoxicity. Our results suggest that neuroprotective effects of agmatine on RGCs under oxidative stress may be mainly attributed to the alpha 2-adrenergic receptor signaling pathway.
胍丁胺对视网膜神经节细胞（RGC）以及皮质和脊髓神经元具有神经保护作用。即使在损伤时不存在，它也能保护 RGC 免受氧化应激。由于胍丁胺对各种细胞受体具有高亲和力，我们使用转化的 RGC（RGC-5 细胞系）评估了胍丁胺的保护机制。将分化的 RGC-5 细胞用 100 μM 胍丁胺预处理，并连续暴露于 1.0 mM 过氧化氢（H2O2）。通过测量乳酸脱氢酶（LDH）来确定细胞活力，并评估选择性α2-肾上腺素能受体拮抗剂育亨宾（0-500 nM）和 N-甲基-D-天冬氨酸（NMDA）受体激动剂 NMDA（0-100 μM）的作用。将胍丁胺的保护作用与选择性 NMDA 受体拮抗剂 MK-801 进行了比较。在 H2O2 暴露 16 小时后，LDH 测定显示细胞损失超过 50%，而在用损伤前预处理胍丁胺时，细胞损失减少到约 30%。育亨宾几乎完全抑制了胍丁胺的保护作用，但 NMDA 没有。此外，MK-801（0-100 μM）并未显著减轻 H2O2 诱导的细胞毒性。我们的结果表明，胍丁胺在氧化应激下对 RGC 的神经保护作用可能主要归因于α2-肾上腺素能受体信号通路。
