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Abstract #20588 Published in IGR 10-1
Aloe-emodin suppressed NMDA-induced apoptosis of retinal ganglion cells through regulation of ERK phosphorylation
Lin H-J; Chao P-DL; Huang S-Y; Wan L; Wu C-J; Tsai F-JPhytotherapy Research 2007; 21: 1007-1014
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 extracellular signal-regulated kinase 1/2 (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.
Dr. F.-J. Tsai, Department of Medical Genetics and Pediatrics, China Medical University Hospital, No. 2 Yuh-Der Road, Taichung 404, Taiwan. d0704@www.cmuh.org.tw
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
2.14 Optic disc (Part of: 2 Anatomical structures in glaucoma)
3.6 Cellular biology (Part of: 3 Laboratory methods)