Neuroprotection by fructose-1,6-bisphosphate involves ROS alterations via p38 MAPK/ERK.
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.
Department of Physiology, Ajou University School of Medicine San 5 Woncheon-dong, Yeongtong-gu, Suwon, 443-749, South Korea.
Jee-Young
JY
Park
Eun Joo
EJ
Kim
Kyoung Ja
KJ
Kwon
Yi-Sook
YS
Jung
Chang-Hyun
CH
Moon
Soo Hwan
SH
Lee
Eun Joo
EJ
Baik
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005635:Fructosediphosphates / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D005635:Fructosediphosphates; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D016202:N-Methylaspartate; D007770:L-Lactate Dehydrogenase; D048051:p38 Mitogen-Activated Protein Kinases; D010751:Phosphopyruvate Hydratase; C029063:fructose-1,6-diphosphate