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Related Experiment Videos

Acidosis reduces neuronal apoptosis

L Xu1, A J Glassford, A J Giaccia

  • 1Department of Anesthesia, Stanford University School of Medicine, CA 94305, USA.

Neuroreport
|May 14, 1998
PubMed
Summary

Extracellular acidosis, a condition of low pH, protects neurons and fibroblasts from cell death, regardless of p53 gene status. This finding suggests acidity can be a protective factor against apoptosis in various cell types.

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Oncology

Background:

  • Acidosis, characterized by low extracellular pH, is frequently observed in conditions such as tissue ischemia and solid tumors.
  • Understanding the role of acidosis in cellular survival, particularly in the context of apoptosis, is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the protective effects of extracellular acidosis on neuronal and fibroblast cell death induced by serum deprivation and hypoxia.
  • To determine if the tumor suppressor protein p53 influences the protective capacity of acidosis against apoptosis.

Main Methods:

  • Primary murine neurons and transformed mouse embryo fibroblasts (p53+/+ and p53-/-) were subjected to serum deprivation or hypoxia.
  • Extracellular pH was modulated to acidic levels (pH 6.0-6.8) to assess its impact on cell viability and death morphology.

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  • Apoptosis and necrosis were evaluated using morphological assessments and potentially other cell death assays.

    • Main Results:

    • Extracellular acidosis at pH 6.0 and 6.4 significantly protected cultured primary murine neurons from serum deprivation-induced apoptotic death.
    • Both p53+/+ and p53-/- fibroblasts exhibited marked protection from serum deprivation-induced cell death under acidic conditions.
    • Hypoxia-induced fibroblast injury was reduced at pH 6.8, with a shift from apoptotic to necrotic morphology observed at lower pH.
    • Acidosis demonstrated a protective effect against apoptosis in both normal and transformed cells, independent of p53 status.

    Conclusions:

    • Extracellular acidosis confers significant protection against apoptosis in both neuronal and fibroblast cells.
    • The protective effect of acidosis is independent of the p53 tumor suppressor gene.
    • Acidosis may represent a novel therapeutic target for mitigating cell death in ischemic and tumor microenvironments.