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Neuroprotection by fructose-1,6-bisphosphate involves ROS alterations via p38 MAPK/ERK.

Authors
Park, JY; Kim, EJ; Kwon, KJ; Jung, YS; Moon, CH; Lee, SH; Baik, EJ
Citation
Brain research, 1026(2):295-301, 2004
Journal Title
Brain research
ISSN
0006-89931872-6240
Abstract
Fructose-1,6-bisphosphate (FBP) is a glucose metabolism intermediate that shows a neuroprotective action in animal models of ischemia and other injuries. The intracellular mechanism of FBP on neuroprotection has not been previously defined. Here, we examined whether FBP has a neuroprotective effect against excitotoxicity, and whether it affects the production of reactive oxygen species (ROS), which are involved in the MAPK pathway in cortical neurons. FBP prevented neuronal death in a dose-dependent manner following 24 h of treatment with the excitotoxin, NMDA. After 8 h of NMDA treatment, we observed FBP-induced inhibition of the production of intracellular ROS, and at the earlier time FBP suppressed NMDA-induced p-p38 and p-ERK expression. In addition, MAPK inhibitors reduced NMDA-induced excitotoxicity and also ROS production. Taken together, our results suggest that the neuroprotective effects of FBP could be explained by down-regulation of free radical production through the p38MAPK/ERK pathway.
MeSH terms
AnimalsBlotting, Western/methodsBrain/cytologyCell Count/methodsCell Death/drug effectsCells, CulturedDose-Response Relationship, DrugDrug InteractionsEmbryo, MammalianEnzyme Inhibitors/pharmacologyFructosediphosphates/*pharmacologyImmunohistochemistry/methodsIntracellular Membranes/drug effects/metabolismL-Lactate Dehydrogenase/metabolismMAP Kinase Signaling System/drug effects/*physiologyMiceMice, Inbred ICRN-Methylaspartate/toxicityNeurons/*drug effectsNeuroprotective Agents/*pharmacologyPhosphopyruvate Hydratase/metabolismReactive Oxygen Species/*metabolismp38 Mitogen-Activated Protein Kinases/*metabolism
DOI
10.1016/j.brainres.2004.08.039
PMID
15488492
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
권, 경자정, 이숙문, 창현이, 수환백, 은주
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