Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.2.3 (glutathione synthetase)
 678 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Molecular mechanism of decreased glutathione content in human immunodeficiency virus type 1 Tat-transgenic mice. 1065 68

Increasing evidence suggests that glutathione (GSH) synthesis is a regulated process. Documented increases in gamma-glutamylcysteine synthetase (GCS) occur in response to oxidants, in tumors, on plating cells at a low cell density, and with nerve growth factor stimulation, suggesting that GSH synthesis may be related to the cell growth and transformation. Previously, extracellular acidic fibroblast growth factor (FGF-1) has been demonstrated to cause transformation and aggressive cell growth in murine embryonic fibroblasts. In the present investigation, we sought to determine whether FGF-1, with its growth inducing properties, resulted in the modulation of GSH biosynthetic enzymes, GCS and GSH synthetase. Murine fibroblasts transduced with (hst/KS)FGF-1, a chimeric human FGF-1 gene containing a signal peptide sequence for secretion, displayed elevated gene expression of both heavy and light subunits of GCS. Activity of GSH synthetase was also elevated in these cells compared with control cells. Nonetheless, GSH was decreased in the FGF-1-transduced cells along with high energy phosphates, adenine nucleotides, NADH, and the redox poise. However, GSSG was not elevated in these cells. Fibroblasts stably expressing human immunodeficiency virus type 1 Tat, which induces intrinsic FGF-1 secretion, resulted in similar changes in GCS, GS, and GSH. The results suggest that although increases in the enzymes of GSH synthesis are a common response to growth factors, an increase in GSH content per se is not required for altered cell growth.
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PMID:Modulation of glutathione synthetic enzymes by acidic fibroblast growth factor. 1068 68

We demonstrated that the levels of enzymes responsible for the synthesis of glutathione (GSH) such as glutathione synthase (GSS), glutamate-cysteine ligase-catalytic subunit (GCLC), and glutathione reductase (GSR) were significantly reduced in the red blood cells (RBCs) isolated from individuals with human immunodeficiency virus (HIV) infection and this reduction correlated with decreased levels of intracellular GSH. GSH content in RBCs can be used as a marker for increased overall oxidative stress and immune dysfunctions caused by HIV infection. Our data supports our hypothesis that compromised levels of GSH in HIV infected individuals' is due to decreased levels of GSH-synthetic enzymes. The role of GSH in combating oxidative stress and improving the functions of immune cells in HIV patients' indicates the benefit of an antioxidant supplement which can reduce the cellular damage and promote the functions of immune cells.
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PMID:Glutathione synthesis is compromised in erythrocytes from individuals with HIV. 2478 76