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Neuroprotective Effect of D-Fructose-1,6-Bisphosphate against beta-Amyloid Induced Neurotoxicity in Rat Hippocampal Organotypic Slice Culture : Involvement of PLC and MEK/ERK Signaling Pathways

English (英語)

The Kobe journal of the medical sciences

51(5/6)

73-83

Kobe University School of Medicine

2006-01

2006-07-15

D-fructose-1,6-bisphosphate (FBP) is an endogenous intermediate of glycolyticpathway which has potent neuroprotective effect against various neurotoxic insults.This study examined whether FBP could antagonize the neurotoxicity induced byamyloid β-peptide (Aβ) in rat hippocampal organotypic slice cultures, and the possiblemechanism was also explored. Treatment with FBP (concentration ranges from 1.7 mMto 10 mM) significantly decreased the cell death in hippocampal slices in the presence ofAβ at 24h, 48h and 72h, and this neuroprotective effect of FBP against Aβ was not in adose-dependent manner, FBP 3.5 mM has better neuroprotective effect than that ofother FBP concentration groups. Treatment with FBP slightly but significantlyincreases the ATP levels in hippocampal slices in the presence of Aβ. However, theincrement of ATP levels was similar among various FBP concentration groups.Neuroprotective effect of FBP 3.5 mM against Aβ induced neurotoxicity inhippocampal slices was attenuated by addition of phospholipase C (PLC) inhibitor,U73122, mitogen activated extracellular signal protein kinase (MEK) inhibitor, U0126,or extracellular signal activated protein kinase (ERK) inhibitor, PD98059 at 24h, 48hand 72h. However, co-treatment with these three kinds of inhibitors did not change theFBP's effect on ATP levels. Our results suggested FBP has neuroprotective effectagainst Aβ induced neurotoxicity in hippocampal slice cultures, and FBP plays role notonly as an alternative energy source, but also a modulator of PLC and MEK/ERKpathways to regulate the cellular response and survival.

Extracellular signal activated protein kinase

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