       Document 0142
 DOCN  M9470142
 TI    Valproic acid reduces the intracellular level of glutathione and
       stimulates human immunodeficiency virus.
 DT    9409
 AU    Simon G; Moog C; Obert G; Laboratoire commun Universite Louis
       Pasteur/Synthelabo,; Strasbourg, France.
 SO    Chem Biol Interact. 1994 Jun;91(2-3):111-21. Unique Identifier :
       AIDSLINE MED/94251837
 AB    Modifications of the glutathione (GSH) intracellular level have been
       implicated in the regulation of human immunodeficiency virus (HIV)
       transcription and expression. In regard to this hypothesis, we have
       investigated the effects of valproic acid (VPA) on HIV replication.
       Indeed, it has been recently reported that VPA inhibits the human red
       blood cell glutathione reductase. In the supernatant of a CEM-SS
       T-lymphocytic cell line infected with the LAI strain of HIV-1, we
       observed an increase, in a dose-dependent fashion, of the reverse
       transcriptase activity after treatment of cells with VPA. VPA also
       induced HIV expression in the chronically infected monocytic U1 cell
       line which constitutively expresses low levels of virus, enhanced the
       HIV-long terminal repeat (LTR)-directed expression of beta-galactosidase
       in transiently transfected Jurkat T-cells, and potentiated the PMA
       effect on the LTR transactivation. GSH assays showed that VPA treatment
       led to a decrease in the intracellular level of this thiol compound in
       U937 (U1 parent-cell line) and in Jurkat T-cells. Work to understand the
       molecular mechanism of VPA-induced HIV transcription and expression are
       now in progress. VPA seems to be an adequate molecule to study the
       implications of a GSH decrease in the stimulation of HIV replication.
       However, a modification of the intracellular balance between reduced and
       oxidized glutathione, rather than a simple reduction of the
       intracellular glutathione level, could be of importance in the
       regulation of HIV replication and we are now testing this hypothesis.
       Finally, these findings already suggest that VPA, which is an
       anticonvulsive drug frequently prescribed for the management of various
       seizure disorders, should not be recommended for treatment of epilepsy
       or other related illnesses in HIV-positive individuals.
 DE    beta-Galactosidase/GENETICS  Cell Line  Gene Expression Regulation,
       Viral/DRUG EFFECTS  Glutathione/*METABOLISM  Granulocyte-Macrophage
       Colony-Stimulating Factor/PHARMACOLOGY  Human  HIV Long Terminal
       Repeat/DRUG EFFECTS  HIV-1/*DRUG EFFECTS/GENETICS/PHYSIOLOGY
       Interleukin-6/PHARMACOLOGY  Monocytes/DRUG
       EFFECTS/METABOLISM/*MICROBIOLOGY  Oxidation-Reduction  Reverse
       Transcriptase/METABOLISM  T-Lymphocytes/DRUG
       EFFECTS/METABOLISM/*MICROBIOLOGY  Tetradecanoylphorbol
       Acetate/PHARMACOLOGY  Transfection  Tumor Cells, Cultured  Tumor
       Necrosis Factor/PHARMACOLOGY  Valproic Acid/*PHARMACOLOGY  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).

