Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity

Kamal M. Yakoub, Giacomo Lazzarino, Angela M. Amorini, Giuseppe Caruso, Concetta Scazzone, Marcello Ciaccio, Barbara Tavazzi, Giuseppe Lazzarino, Antonio Belli, Valentina Di Pietro

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume20
Issue number9
DOIs
Publication statusPublished - May 7 2019

Fingerprint

Fructose
Adenosinetriphosphate
N-Methylaspartate
rats
Administrative data processing
Rats
metabolism
Brain
adenosine triphosphate
Metabolism
aldolase
Phosphates
brain
Phosphofructokinases
adenosine diphosphate
cells
Fructose-Bisphosphate Aldolase
Glyceraldehyde-3-Phosphate Dehydrogenases
dehydrogenases
necrosis

Keywords

  • energy metabolism
  • excitotoxicity
  • fructose-1,6-bisphosphate
  • mitochondrial dysfunction
  • N-methyl-d-aspartate
  • organotypic hippocampal brain slice cultures

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Yakoub, K. M., Lazzarino, G., Amorini, A. M., Caruso, G., Scazzone, C., Ciaccio, M., ... Di Pietro, V. (2019). Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity. International Journal of Molecular Sciences, 20(9). https://doi.org/10.3390/ijms20092239

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, 07.05.2019.

Research output: Contribution to journalArticle

Yakoub, KM, Lazzarino, G, Amorini, AM, Caruso, G, Scazzone, C, Ciaccio, M, Tavazzi, B, Lazzarino, G, Belli, A & Di Pietro, V 2019, 'Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity', International Journal of Molecular Sciences, vol. 20, no. 9. https://doi.org/10.3390/ijms20092239
Yakoub, Kamal M. ; Lazzarino, Giacomo ; Amorini, Angela M. ; Caruso, Giuseppe ; Scazzone, Concetta ; Ciaccio, Marcello ; Tavazzi, Barbara ; Lazzarino, Giuseppe ; Belli, Antonio ; Di Pietro, Valentina. / Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity. In: International Journal of Molecular Sciences. 2019 ; Vol. 20, No. 9.
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