Role of 7,8-dihydroneopterin in T-cell apoptosis and HTLV-1 transcription in vitro

Oncogene. 1996 Nov 21;13(10):2281-5.

Abstract

Adult T-cell leukemia is associated with high levels of neopterin, released in large amounts from human macrophages upon stimulation with interferon-gamma. Recent data suggested a potential role of neopterin-derivatives in oxygen radical-mediated processes, and evidence accumulates that oxidative stress is involved in the pathogenesis of viral diseases. We now report that increased concentrations of 7,8-dihydroneopterin may lead to enhanced apoptosis and disturbance of the redox-balance of human leukemic Jurkat T cells. Additionally, we demonstrate that 7,8-dihydroneopterin and hydrogen peroxide activate the type 1 human T-cell leukemia virus (HTLV-1) long terminal repeat (LTR). Furthermore, we found that the activity of the HTLV-1 transactivator protein Tax is amplified by an elevated concentration of 7,8-dihydroneopterin. Tax did not significantly augment 7,8-dihydroneopterin mediated apoptosis. Based on our data we propose that 7,8-dihydroneopterin may be involved in the progression to higher stages of HTLV-1 associated disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Gene Products, tax / genetics
  • Gene Products, tax / metabolism
  • Human T-lymphotropic virus 1 / genetics*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Neopterin / analogs & derivatives
  • Oxidation-Reduction
  • Pteridines / pharmacology*
  • Repetitive Sequences, Nucleic Acid / drug effects*
  • T-Lymphocytes / drug effects*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antioxidants
  • Gene Products, tax
  • Pteridines
  • 7,8-dihydroneopterin
  • Neopterin
  • Hydrogen Peroxide