Acidosis has opposite effects on neuronal survival during hypoxia and reoxygenation

Runar Almaas, Morten Pytte, Julie K. Lindstad, Marianne Wright, Ola Didrik Saugstad, David E Pleasure, Terje Rootwelt

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

To study the effect of extracellular acidosis on apoptosis and necrosis during ischemia and reoxygenation, we exposed human post-mitotic NT2-N neurones to oxygen and glucose deprivation (OGD) followed by reoxygenation. In some experiments, pH of the cell medium was lowered to 5.9 during either OGD or reoxygenation or both. Staurosporine, used as a positive control for apoptosis, caused Poly(ADP-ribose)-polymerase (PARP) cleavage and nuclear fragmentation, but no PARP cleavage and little fragmentation were seen after OGD. Low molecular weight DNA fragments were found after staurosporine treatment, but not after OGD. No protective effect of caspase inhibitors was seen after 3 h of OGD and 21 h of reoxygenation, but after 45 h of reoxygenation aspase inhibition induced a modest improvement in 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) cleavage. While acidosis during OGD accompanied by neutral medium during reoxygenation protected the neurones (MTT: 228 ± 117% of neutral medium, p < 0.001), acidosis during reoxygenation only was detrimental (MTT: 38 ± 25%, p < 0.01). We conclude that apoptotic mechanisms play a minor role after OGD in NT2-N neurones. The effect of acidosis on neuronal survival depends on the timing of acidosis, as acidosis was protective during OGD and detrimental during reoxygenation.

Original languageEnglish (US)
Pages (from-to)1018-1027
Number of pages10
JournalJournal of Neurochemistry
Volume84
Issue number5
DOIs
StatePublished - Mar 2003
Externally publishedYes

Keywords

  • Acidosis
  • Apoptosis
  • Human
  • Ischemia
  • Neurone
  • Reoxygenation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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