Role of 7,8-dihydroneopterin in T-cell apoptosis and HTLV-1 transcription in vitro.
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.
Baier-Bitterlich
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G
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Baier
G
G
Fuchs
D
D
Böck
G
G
Hausen
A
A
Utermann
G
G
Pavelka
M
M
Wachter
H
H
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019798:Neopterin / Q000031:analogs & derivatives; D010084:Oxidation-Reduction; D011621:Pteridines / Q000494:pharmacology*; D012091:Repetitive Sequences, Nucleic Acid / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D016356:Gene Products, tax; D011621:Pteridines; C000976:7,8-dihydroneopterin; D019798:Neopterin; D006861:Hydrogen Peroxide