Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity
Research output: Contribution to journal › Article › peer-review
Standard
Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity. / Yakoub, Kamal M; Lazzarino, Giacomo; Amorini, Angela M; Caruso, Giuseppe; Scazzone, Concetta; Ciaccio, Marcello; Tavazzi, Barbara; Lazzarino, Giuseppe; Belli, Antonio; Di Pietro, Valentina.
In: International Journal of Molecular Sciences, Vol. 20, No. 9, 2239, 07.05.2019.Research output: Contribution to journal › Article › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity
AU - Yakoub, Kamal M
AU - Lazzarino, Giacomo
AU - Amorini, Angela M
AU - Caruso, Giuseppe
AU - Scazzone, Concetta
AU - Ciaccio, Marcello
AU - Tavazzi, Barbara
AU - Lazzarino, Giuseppe
AU - Belli, Antonio
AU - Di Pietro, Valentina
PY - 2019/5/7
Y1 - 2019/5/7
N2 - Effects of fructose 1,6-bisphosphate (F-1,6-P2) towards N-methyl-d-aspartate NMDA excitotoxicity were evaluated in rat organotypic hippocampal brain slice cultures (OHSC) challenged for 3 h with 30 μM NMDA, followed by incubations (24, 48, and 72 h) without (controls) and with F-1,6-P2 (0.5, 1 or 1.5 mM). At each time, cell necrosis was determined by measuring LDH in the medium. Energy metabolism was evaluated by measuring ATP, GTP, ADP, AMP, and ATP catabolites (nucleosides and oxypurines) in deproteinized OHSC extracts. Gene expressions of phosphofructokinase, aldolase, and glyceraldehyde-3-phosphate dehydrogenase were also measured. F-1,6-P2 dose-dependently decreased NMDA excitotoxicity, abolishing cell necrosis at the highest concentration tested (1.5 mM). Additionally, F-1,6-P2 attenuated cell energy imbalance caused by NMDA, ameliorating the mitochondrial phosphorylating capacity (increase in ATP/ADP ratio) Metabolism normalization occurred when using 1.5 mM F-1,6-P2. Remarkable increase in expressions of phosphofructokinase, aldolase and glyceraldehyde-3-phosphate dehydrogenase (up to 25 times over the values of controls) was also observed. Since this phenomenon was recorded even in OHSC treated with F-1,6-P2 with no prior challenge with NMDA, it is highly conceivable that F-1,6-P2 can enter into intact cerebral cells producing significant benefits on energy metabolism. These effects are possibly mediated by changes occurring at the gene level, thus opening new perspectives for F-1,6-P2 application as a useful adjuvant to rescue mitochondrial metabolism of cerebral cells under stressing conditions.
AB - Effects of fructose 1,6-bisphosphate (F-1,6-P2) towards N-methyl-d-aspartate NMDA excitotoxicity were evaluated in rat organotypic hippocampal brain slice cultures (OHSC) challenged for 3 h with 30 μM NMDA, followed by incubations (24, 48, and 72 h) without (controls) and with F-1,6-P2 (0.5, 1 or 1.5 mM). At each time, cell necrosis was determined by measuring LDH in the medium. Energy metabolism was evaluated by measuring ATP, GTP, ADP, AMP, and ATP catabolites (nucleosides and oxypurines) in deproteinized OHSC extracts. Gene expressions of phosphofructokinase, aldolase, and glyceraldehyde-3-phosphate dehydrogenase were also measured. F-1,6-P2 dose-dependently decreased NMDA excitotoxicity, abolishing cell necrosis at the highest concentration tested (1.5 mM). Additionally, F-1,6-P2 attenuated cell energy imbalance caused by NMDA, ameliorating the mitochondrial phosphorylating capacity (increase in ATP/ADP ratio) Metabolism normalization occurred when using 1.5 mM F-1,6-P2. Remarkable increase in expressions of phosphofructokinase, aldolase and glyceraldehyde-3-phosphate dehydrogenase (up to 25 times over the values of controls) was also observed. Since this phenomenon was recorded even in OHSC treated with F-1,6-P2 with no prior challenge with NMDA, it is highly conceivable that F-1,6-P2 can enter into intact cerebral cells producing significant benefits on energy metabolism. These effects are possibly mediated by changes occurring at the gene level, thus opening new perspectives for F-1,6-P2 application as a useful adjuvant to rescue mitochondrial metabolism of cerebral cells under stressing conditions.
KW - Animals
KW - Energy Metabolism
KW - Fructose-Bisphosphatase/pharmacology
KW - Fructose-Bisphosphate Aldolase/metabolism
KW - Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism
KW - Hippocampus/drug effects
KW - N-Methylaspartate/toxicity
KW - Necrosis
KW - Neuroprotective Agents/pharmacology
KW - Phosphofructokinases/metabolism
KW - Purine Nucleosides/metabolism
KW - Rats
KW - Rats, Wistar
U2 - 10.3390/ijms20092239
DO - 10.3390/ijms20092239
M3 - Article
C2 - 31067671
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 9
M1 - 2239
ER -