Fructose-1,6-bisphosphate protects hippocampal rat slices from NMDA excitotoxicity

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

Risultato della ricerca: Article

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 M 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.
Lingua originaleEnglish
pagine (da-a)2239-
Numero di pagine16
RivistaInternational Journal of Molecular Sciences
Volume20
Stato di pubblicazionePublished - 2019

All Science Journal Classification (ASJC) codes

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

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    Ciaccio, M., Scazzone, C., Belli, A., Di Pietro, V., Scazzone, C., Ciaccio, M., Lazzarino, G., Caruso, G., Yakoub, K. M., Amorini, A. M., Tavazzi, B., & Lazzarino, G. (2019). Fructose-1,6-bisphosphate protects hippocampal rat slices from NMDA excitotoxicity. International Journal of Molecular Sciences, 20, 2239-.