Document 0132
 DOCN  M9470132
 TI    Effects of glutathione precursors on human immunodeficiency virus
       replication.
 DT    9409
 AU    Simon G; Moog C; Obert G; Laboratoire common Universite Louis
       Pasteur/Synthelabo,; Strasbourg, France.
 SO    Chem Biol Interact. 1994 Jun;91(2-3):217-24. Unique Identifier :
       AIDSLINE MED/94251848
 AB    Asymptomatic human immunodeficiency virus (HIV)-seropositive individuals
       have reduced glutathione (GSH) levels. This has led to the suggestion
       that elevated intracellular thiols levels may inhibit HIV replication
       and progression of the disease. We confirmed that N-acetyl-L-cysteine
       (NAC), a cysteine prodrug which maintains intracellular GSH levels
       during oxidative stress, inhibits in the chronically infected U1 cells,
       the stimulation of HIV replication induced by phorbol 12-myristate
       13-acetate (PMA), interleukin-6 (IL-6) or granulocyte-macrophage colony
       stimulating factor (GM-CSF). However, we found no significant inhibition
       of PMA-mediated long terminal repeat (LTR)-directed beta-galactosidase
       expression in transiently transfected Jurkat T-cells. We have compared
       NAC effects with the effects of other GSH precursors on HIV expression.
       Treatment of the U1 cell line by L-2-oxo-4-thiazolidine carboxylic acid
       (OTC), which is converted to cysteine by 5-oxoprolinase, or by
       homocysteine (HC), a natural cysteine precursor, reduced the PMA-induced
       HIV expression, but surprisingly, markedly stimulated the expression
       mediated by IL-6 and GM-CSF. Several experiments to investigate the
       effect of OTC on LTR transactivation were carried out, but
       beta-galactosidase activity was never modified in a significant fashion
       in PMA-induced Jurkat T-cells after OTC treatment. Furthermore, HC
       stimulated the PMA-mediated HIV-LTR transactivation in Jurkat T-cells.
       GSH assays showed that treatment of U937 and Jurkat T-cells with NAC and
       OTC moderately increased the GSH level, while HC led to a significantly
       higher increase of the thiol level. In conclusion, it appeared that an
       increase of the GSH intracellular level did not lead solely to an
       inhibition of HIV replication but could also lead to an activation of
       viral expression. This seemed the case when HIV replication was
       stimulated by compounds which act mainly at a post-transcriptional
       level.
 DE    beta-Galactosidase/BIOSYNTHESIS  Acetylcysteine/*PHARMACOLOGY  Cell Line
       Colorimetry  Comparative Study  Gene Expression Regulation, Viral/DRUG
       EFFECTS  Glutathione/*METABOLISM  Granulocyte-Macrophage
       Colony-Stimulating Factor/PHARMACOLOGY  Homocysteine/*PHARMACOLOGY
       Human  HIV/*DRUG EFFECTS/GENETICS/PHYSIOLOGY  HIV Long Terminal
       Repeat/DRUG EFFECTS  Interleukin-6/PHARMACOLOGY  Prodrugs/PHARMACOLOGY
       Tetradecanoylphorbol Acetate/PHARMACOLOGY  Thiazoles/*PHARMACOLOGY
       Tumor Cells, Cultured  Virus Replication/DRUG EFFECTS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).