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Acidosis has opposite effects on neuronal survival during hypoxia and reoxygenation
Author(s) -
Almaas Runar,
Pytte Morten,
Lindstad Julie K.,
Wright Marianne,
Saugstad Ola Didrik,
Pleasure David,
Rootwelt Terje
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01593.x
Subject(s) - staurosporine , acidosis , apoptosis , dna fragmentation , hypoxia (environmental) , poly adp ribose polymerase , biology , extracellular , ischemia , programmed cell death , medicine , endocrinology , pharmacology , microbiology and biotechnology , biochemistry , chemistry , oxygen , polymerase , dna , protein kinase c , enzyme , organic chemistry
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 caspase 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.