Impairment of the mitochondrial electron chain transport prevents NF-kappa B activation by hydrogen peroxide

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C Josse1, S Legrand-Poels, B Piret

  • 1Laboratory of Fundamental Virology, University of Liège, Belgium.

Free Radical Biology & Medicine
|July 9, 1998
PubMed

Insights

Mitochondrial electron transport chain inhibition blocks NF-kappa B activation by hydrogen peroxide (H2O2) in lymphocytes. This suggests reactive oxygen species (ROS) generated by mitochondria are crucial for this specific signaling pathway.

Area of Science:

  • Cellular Biology
  • Immunology
  • Biochemistry

Background:

  • Nuclear factor kappa B (NF-kappa B) activation is critical in cellular responses.
  • Reactive oxygen species (ROS) are implicated in NF-kappa B signaling.
  • The precise role of mitochondrial function in NF-kappa B activation requires further elucidation.

Purpose of the Study:

  • To investigate the role of mitochondrial electron transport chain and ATP production in NF-kappa B activation.
  • To determine if hydrogen peroxide (H2O2)-induced NF-kappa B activation is dependent on mitochondrial respiration.

Main Methods:

  • Inhibition of mitochondrial electron transport chain using rotenone and antimycin A.
  • Assessment of NF-kappa B translocation induced by H2O2, tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharide (LPS).
  • Measurement of cellular ATP levels and oxygen consumption in lymphocytes.

Main Results:

  • Rotenone and antimycin A dose-dependently inhibited H2O2-induced NF-kappa B translocation.
  • Mitochondrial inhibitors did not affect NF-kappa B activation by TNF-alpha or LPS.
  • Oligomycin and FCCP also inhibited H2O2-induced NF-kappa B activation, correlating with reduced oxygen consumption.
  • H2O2 caused a transient ATP drop, significantly enhanced by oligomycin, highlighting ATP's role.

Conclusions:

  • Mitochondrial respiration is essential for H2O2-induced NF-kappa B activation in lymphocytes.
  • ATP generated through mitochondrial respiration plays a key role in this specific signaling pathway.
  • NF-kappa B activation by other stimuli like TNF-alpha and LPS is independent of mitochondrial respiration.

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