Hypoglycaemia-induced cell death: Features of neuroprotection by the P2 receptor antagonist basilen blue

Fabio Cavaliere, Nadia D'Ambrosi, Giuseppe Sancesario, Giorgio Bernardi, Cinzia Volonté

Research output: Contribution to journalArticle

Abstract

Our previous work in neuronal cultures has shown that several antagonists of P2 ATP receptors prevent cell death evoked by hypoglycaemia, chemical hypoxia, mitochondria dysfunction, as well as glutamate-dependent excitotoxicity and low potassium-induced apoptosis. Experiments are now designed to examine which biological pathway contributes to cell death/survival under glucose starvation. We show here that, consequently to hypoglycaemic insults, cerebellar granule neurones undergo a combination of apoptosis and necrosis both inhibited by the P2 receptor antagonist basilen blue. This is demonstrated by morphological and biochemical features, such as TdT-mediated dUTP-biotin nick end-labelling, fluorescent staining of nuclear chromatin using Hoechst 33258, direct counting of intact viable nuclei and extracellular releasing of the cytosolic enzyme LDH. Furthermore, we show that hypoglycaemia induces outflow of cytochrome c from mitochondria and it up-regulates heat-shock proteins HSP70, but not HSP90, glucose-regulated proteins GRP75 and GRP78, as well as expression and activity of the enzyme caspase-2. Basilen blue can modulate only some of these effects. Our data contribute to dissect the role played by P2 receptor antagonism in sustaining neuroprotection against metabolic stresses. (C) 2001 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)199-207
Number of pages9
JournalNeurochemistry International
Volume38
Issue number3
DOIs
Publication statusPublished - 2001

Keywords

  • Apoptosis
  • Bcl-2
  • Caspase-2
  • Cytochrome c
  • GRP75-78
  • HSP70 protein
  • Necrosis

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

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