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Nucleotide changes in oxidatively stressed lymphocytes

G P Palace1, D A Lawrence

  • 1Department of Pharmacology and Toxicology, Albany Medical College, NY 12208, USA.

Journal of Biochemical Toxicology
|June 1, 1995
PubMed
Summary
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Oxidative stress impairs thymus-derived lymphocyte (T cell) DNA synthesis and proliferation by reducing key nucleotide biosynthesis. This suggests a potential mechanism for T cell dysfunction in various conditions.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Oxidative stress is implicated in T cell dysfunction, similar to HIV-1 effects.
  • Understanding molecular mechanisms behind T cell suppression is crucial.

Purpose of the Study:

  • To investigate the impact of oxidative stress on nucleotide pools in T cells.
  • To explore the role of glutathione (GSH) synthesis inhibition in this process.

Main Methods:

  • Peripheral blood lymphocytes were stimulated with OKT3.
  • Cells were preincubated with buthionine sulfoximine to inhibit GSH synthesis.
  • The effect on nucleotide biosynthesis (dUDP, TTP) was measured using 3H-uridine.

Main Results:

Related Experiment Videos

  • Inhibition of GSH synthesis led to significant reductions in dUDP and TTP biosynthesis.
  • This occurred after 18-32 hours of stimulation in oxidatively stressed T cells.
  • Conclusions:

    • Oxidative stress, exacerbated by GSH inhibition, impairs T cell nucleotide synthesis.
    • Reduced nucleotide biosynthesis may indicate impaired ribonucleotide reductase activity, contributing to T cell suppression.