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

Jee-Young Park; Eun Joo Kim; Kyoung Ja Kwon; Yi-Sook Jung; Chang-Hyun Moon; Soo Hwan Lee; Eun Joo Baik

doi:10.1016/j.brainres.2004.08.039

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

Brain Res. 2004 Nov 12;1026(2):295-301. doi: 10.1016/j.brainres.2004.08.039.

Authors

Jee-Young Park¹, Eun Joo Kim, Kyoung Ja Kwon, Yi-Sook Jung, Chang-Hyun Moon, Soo Hwan Lee, Eun Joo Baik

Affiliation

¹ Department of Physiology, Ajou University School of Medicine San 5 Woncheon-dong, Yeongtong-gu, Suwon, 443-749, South Korea.

PMID: 15488492
DOI: 10.1016/j.brainres.2004.08.039

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blotting, Western / methods
Brain / cytology
Cell Count / methods
Cell Death / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Drug Interactions
Embryo, Mammalian
Enzyme Inhibitors / pharmacology
Fructosediphosphates / pharmacology*
Immunohistochemistry / methods
Intracellular Membranes / drug effects
Intracellular Membranes / metabolism
L-Lactate Dehydrogenase / metabolism
MAP Kinase Signaling System / drug effects
MAP Kinase Signaling System / physiology*
Mice
Mice, Inbred ICR
N-Methylaspartate / toxicity
Neurons / drug effects*
Neuroprotective Agents / pharmacology*
Phosphopyruvate Hydratase / metabolism
Reactive Oxygen Species / metabolism*
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Enzyme Inhibitors
Fructosediphosphates
Neuroprotective Agents
Reactive Oxygen Species
N-Methylaspartate
L-Lactate Dehydrogenase
p38 Mitogen-Activated Protein Kinases
Phosphopyruvate Hydratase
fructose-1,6-diphosphate