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.
D-fructose-1,6-bisphosphate (FBP) is an endogenous intermediate of glycolytic pathway which has potent neuroprotective effect against various neurotoxic insults. This study examined whether FBP could antagonize the neurotoxicity induced by amyloid beta-peptide (Abeta) in rat hippocampal organotypic slice cultures, and the possible mechanism was also explored. Treatment with FBP (concentration ranges from 1.7 mM to 10 mM) significantly decreased the cell death in hippocampal slices in the presence of Abeta at 24h, 48 h and 72 h, and this neuroprotective effect of FBP against Abeta was not in a dose-dependent manner, FBP 3.5 mM has better neuroprotective effect than that of other FBP concentration groups. Treatment with FBP slightly but significantly increases the ATP levels in hippocampal slices in the presence of Abeta. However, the increment of ATP levels was similar among various FBP concentration groups. Neuroprotective effect of FBP 3.5 mM against Abeta induced neurotoxicity in hippocampal 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 24 h, 48 h and 72 h. However, co-treatment with these three kinds of inhibitors did not change the FBP's effect on ATP levels. Our results suggested FBP has neuroprotective effect against Abeta induced neurotoxicity in hippocampal slice cultures, and FBP plays role not only as an alternative energy source, but also a modulator of PLC and MEK/ERK pathways to regulate the cellular response and survival.
Song
Xiuzhen
X
Division of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine.
Wu
Bin
B
Takata
Toshihiro
T
Wang
Xiaonan
X
Oizumi
Ximena-Sayuri
XS
Akisaki
Taichi
T
Yokono
Koichi
K
Sakurai
Takashi
T
D000255:Adenosine Triphosphate / Q000032:analysis; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005635:Fructosediphosphates / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D020930:MAP Kinase Kinase Kinases / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D010738:Type C Phospholipases / Q000502:physiology*
D016229:Amyloid beta-Peptides; D005635:Fructosediphosphates; D018696:Neuroprotective Agents; D000255:Adenosine Triphosphate; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; D010738:Type C Phospholipases; C029063:fructose-1,6-diphosphate