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Related Experiment Videos

Thiol modification and cell signalling in chemical toxicity.

P Nicotera1, J M Dypbukt, A D Rossi

  • 1Department of Toxicology, Karolinska Institutet Stockholm, Sweden.

Toxicology Letters
|December 1, 1992
PubMed
Summary

Oxidative stress from thiol oxidizing agents can impact cell signaling. Depending on the concentration, oxidants may promote cell growth and proliferation or trigger programmed cell death and necrosis.

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Thiol oxidizing agents modify proteins crucial for cell signaling pathways.
  • These modifications can disrupt normal cell metabolism, growth, and responses to stimuli.
  • Aberrant signaling affects phosphoinositide metabolism, protein kinase activation, and intracellular calcium levels.

Purpose of the Study:

  • To investigate the dose-dependent effects of oxidants on cell signaling and cellular fate.
  • To determine how varying oxidant concentrations influence cell proliferation, differentiation, and death.
  • To elucidate the mechanisms by which oxidative stress impacts multiple signaling pathways.

Main Methods:

  • Exposure of cell cultures to varying concentrations of thiol oxidizing agents.

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  • Analysis of key signaling pathway components and their modifications.
  • Assessment of cellular responses including proliferation, differentiation, programmed cell death (PCD), and necrosis.

    • Main Results:

    • Moderate oxidant levels potentiate growth signals, enhancing cell proliferation and differentiation.
    • High oxidant concentrations inhibit growth signals, blocking proliferation and inducing PCD.
    • Significant alterations in signaling pathways and increased catabolic reactions lead to cell death by necrosis.

    Conclusions:

    • Oxidant interaction with cell signaling exhibits dose-dependent, opposing effects.
    • Oxidative stress can either mimic growth factor stimulation or inhibit growth signals, activating distinct cellular outcomes.
    • These findings highlight the complex role of oxidative reactions in regulating cell fate, from proliferation to cell death.