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p53 expression in nitric oxide-induced apoptosis

U K Messmer1, M Ankarcrona, P Nicotera

  • 1University of Konstanz, Faculty of Biology, Germany.

FEBS Letters
|November 21, 1994
PubMed

Insights

Nitric oxide (NO) induces apoptosis by upregulating the tumor suppressor gene p53. Inhibiting NO production prevents p53 expression and cell death, suggesting DNA damage as a key mechanism.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Immunology

Background:

  • Nitric oxide (NO) is a critical signaling molecule in physiological and pathological processes.
  • NO and its byproducts can induce DNA damage, leading to cell death pathways like necrosis and apoptosis.
  • The role of NO in inducing apoptosis requires further elucidation, particularly concerning the involvement of tumor suppressor genes.

Purpose of the Study:

  • To investigate the mechanism by which nitric oxide (NO) induces apoptosis in mammalian cells.
  • To determine the role of the tumor suppressor gene p53 in NO-mediated apoptosis.
  • To explore the relationship between NO generation, p53 expression, and cell death.

Main Methods:

  • Utilized RAW 264.7 macrophages and RINm5F pancreatic cells.
  • Stimulated NO generation using cytokine-induced NO-synthase and NO donor molecules.
  • Administered NO-synthase inhibitors (e.g., NG-monomethyl-L-arginine) to block NO production.
  • Assessed p53 gene expression and apoptosis induction.

Main Results:

  • Nitric oxide (NO) generation stimulated the expression of the tumor suppressor gene p53 in both cell types prior to apoptosis.
  • Inhibition of NO production using NG-monomethyl-L-arginine blocked both inducible NO generation and subsequent p53 expression and apoptosis.
  • These findings indicate a causal link between NO, p53 activation, and apoptosis.

Conclusions:

  • Nitric oxide-induced apoptosis in RAW 264.7 macrophages and RINm5F cells is mediated by the upregulation of the tumor suppressor gene p53.
  • The mechanism involves DNA damage induced by NO, leading to p53 activation and subsequent apoptotic cell death.
  • This study highlights a novel pathway for NO in regulating cell fate through the p53 tumor suppressor.

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