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Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds
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Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds

Published on: February 16, 2022

The nitric oxide-sensitive p21Ras-ERK pathway mediates S-nitrosoglutathione-induced apoptosis

Maristela Tsujita1, Wagner L Batista, Fernando T Ogata

  • 1Departamento de Bioquímica/Biologia Molecular, Centro Interdisciplinar de Terapia Gênica CINTERGEN, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil.

Biochemical and Biophysical Research Communications
|March 8, 2008
PubMed

Insights

Nitric oxide activates p21Ras, a key signaling protein, to induce apoptosis in THP-1 cells. The p21Ras-ERK pathway is crucial for this S-nitrosoglutathione-induced cell death.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Apoptosis Research

Background:

  • p21Ras protein is central to cell signaling, influencing cell cycle progression and apoptosis.
  • Nitric oxide (NO) activates p21Ras via a redox-sensitive cysteine residue (118).
  • S-nitrosoglutathione (SNOG) is a nitric oxide donor with implications in cellular processes.

Purpose of the Study:

  • To investigate the role of the p21Ras-ERK pathway in SNOG-induced apoptosis in THP-1 monocytes/macrophages.
  • To determine which downstream mitogen-activated protein kinase (MAPK) pathways are regulated by p21Ras in response to SNOG.
  • To elucidate the mechanism by which SNOG triggers apoptosis via p21Ras signaling.

Main Methods:

  • Utilized THP-1 cells, including those expressing a nitric oxide-insensitive mutant p21Ras (p21Ras(C118S)).
  • Investigated the activation of ERK, JNK, and p38 MAP kinase pathways.
  • Employed specific inhibitors (PD98059 for ERK) and assessed apoptosis and p21Waf1 expression.

Main Results:

  • SNOG-induced apoptosis in THP-1 cells was significantly reduced in cells expressing NO-insensitive p21Ras.
  • Only the ERK1/2 pathway activation by SNOG was dependent on p21Ras.
  • Inhibition of ERK significantly attenuated SNOG-induced apoptosis and p21Waf1 expression, while JNK and p38 inhibition had minimal effects.

Conclusions:

  • The redox-sensitive p21Ras-ERK pathway is essential for mediating SNOG-induced pro-apoptotic signaling in THP-1 cells.
  • p21Ras acts as a critical sensor and transducer of NO-related apoptotic signals.
  • This pathway regulates both apoptosis induction and p21Waf1 expression in response to SNOG.

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