Aloe-emodin suppressed NMDA-induced apoptosis of retinal ganglion cells through regulation of ERK phosphorylation.
A high concentration of glutamate in the vitreous body and optic nerves of the eyes activates N-methyl-D-aspartate (NMDA) receptors and is toxic to retina ganglion cells (RGCs) in glaucomatous patients. Aloe-emodin sulfates/glucuronides (s/g), the major metabolites of aloe-emodin, was found to be effective in decreasing NMDA-induced apoptosis in RGCs. In order to elucidate the mechanisms, an in vitro optic neuropathy model adding NMDA to N18 RGCs was used in this study. The phosphorylation level of extra-cellular signal-regulated kinase1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 kinase (cytokines-suppressive antiinflammatory drug binding protein kinase) were measured by western blotting and luciferase reporter assay. The results showed that aloe-emodin metabolites significantly decreased the activation of three major mitogen-activated protein (MAP) kinase pathways and the activation of downstream genes in nucleus induced by NMDA, which were verified by the addition of the respective inhibitors. Comparing the effect of the inhibitors of the three MAP kinase pathways, the ERK pathway was found to be the major route of aloe-emodin metabolites in decreasing the apoptosis of NMDA-treated RGCs. Besides, cfos rather then cjun was the target downstream gene. Aloe-emodin emodin metabolites could regulate the phosphorylation of ERK kinases and it was a promising candidate for NMDA-induced apoptosis of RGCs.
Lin
Hui-Ju
HJ
Department of Ophthalmology, China Medical University Hospital, Asia University, Taichung, Taiwan.
Chao
Pei-Dawn Lee
PD
Huang
Shiuan-Yi
SY
Wan
Lai
L
Wu
Chen-Ju
CJ
Tsai
Fuu-Jen
FJ
D000818:Animals; D000880:Anthraquinones / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016202:N-Methylaspartate / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
D000880:Anthraquinones; D016202:N-Methylaspartate; C518327:aloe emodin; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases