Acidosis reduces neuronal apoptosis.
Acidosis is a well established concomitant of tissue ischemia. Acidosis in the pH range 6.0-7.0 is seen in cerebral ischemia and within solid tumors. Extracellular acidosis of pH 6.0 and 6.4 provided essentially complete protection from 48 h serum deprivation induced apoptotic death of cultured primary murine neurons. We tested the effect of p53 using transformed mouse embryo fibroblasts of either p53+/+ or p53-/- genotype. Both were markedly protected from serum deprivation by acidity. Hypoxia induced fibroblast injury was also reduced at pH 6.8. Lower pH resulted in a shift from apoptotic to necrotic morphology after 42 h hypoxia. Acidosis reduces apoptosis of both normal and transformed cells, irrespective of p53 status.
Xu
L
L
Department of Anesthesia, Stanford University School of Medicine, CA 94305, USA.
Glassford
A J
AJ
Giaccia
A J
AJ
Giffard
R G
RG
D000138:Acidosis / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002021:Buffers; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005347:Fibroblasts; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D002021:Buffers; D016895:Culture Media, Serum-Free; D016159:Tumor Suppressor Protein p53