PMID- 10652368
OWN - NLM
STAT- MEDLINE
DCOM- 20000302
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 5
DP  - 2000 Feb 4
TI  - Molecular mechanism of decreased glutathione content in human immunodeficiency
      virus type 1 Tat-transgenic mice.
PG  - 3693-8
AB  - Human immunodeficiency virus (HIV) progressively depletes GSH content in humans. 
      Although the accumulated evidence suggests a role of decreased GSH in the
      pathogenesis of HIV, significant controversy remains concerning the mechanism of 
      GSH depletion, especially in regard to envisioning appropriate therapeutic
      strategies to help compensate for such decreased antioxidant capacity. Tat, a
      transactivator encoded by HIV, is sufficient to cause GSH depletion in vitro and 
      is implicated in AIDS-associated Kaposi's sarcoma and B cell lymphoma. In this
      study, we report a decrease in GSH biosynthesis with Tat, using HIV-1 Tat
      transgenic (Tat+) mice. A significant decline in the total intracellular GSH
      content in liver and erythrocytes of Tat+ mice was accompanied by decreased
      gamma-glutamylcysteine synthetase regulatory subunit mRNA and protein content,
      which resulted in an increased sensitivity of gamma-glutamylcysteine synthetase
      to feedback inhibition by GSH. Further study revealed a significant reduction in 
      the activity of GSH synthetase in liver of Tat+ mice, which was linearly
      associated with their GSH content. Therefore, Tat appears to decrease GSH in
      vivo, at least partially, through modulation of GSH biosynthetic enzymes.
FAU - Choi, J
AU  - Choi J
AD  - Department of Molecular Pharmacology, University of Southern California School of
      Pharmacy, Los Angeles, California 90033, USA.
FAU - Liu, R M
AU  - Liu RM
FAU - Kundu, R K
AU  - Kundu RK
FAU - Sangiorgi, F
AU  - Sangiorgi F
FAU - Wu, W
AU  - Wu W
FAU - Maxson, R
AU  - Maxson R
FAU - Forman, H J
AU  - Forman HJ
LA  - eng
GR  - ES05511/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Gene Products, tat)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
RN  - EC 6.3.2.3 (Glutathione Synthase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
SB  - X
MH  - Animals
MH  - Gene Products, tat/*genetics/metabolism
MH  - Glutathione/genetics/*metabolism
MH  - Glutathione Synthase/genetics/*metabolism
MH  - *HIV-1
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - tat Gene Products, Human Immunodeficiency Virus
EDAT- 2000/02/01 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/01 09:00
PHST- 2000/02/01 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/01 09:00 [entrez]
AID - 10.1074/jbc.275.5.3693 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Feb 4;275(5):3693-8. doi: 10.1074/jbc.275.5.3693.