BACKGROUND Depletion of blood glutathione (GSH), a key antioxidant, is known to occur in preterm infants. OBJECTIVE Our aim was to determine: 1) whether GSH depletion is present at the time of birth; and 2) whether it is associated with insufficient availability of cysteine (cys), the limiting GSH precursor, or a decreased capacity to synthesize GSH. METHODOLOGY Sixteen mothers delivering v...

4-Nitroquinoline 1-oxide (4NQO( is a toxic and carcinogenic compound that has been reported to be subject to conjugation with glutathione (GSH). This reaction may proceed non-enzymatically or be catalyzed by GSH transferases. The non-enzymatic rate for this reaction has been reported to be very high. The purposes of this investigation were todevelop a spectrophotometric assay for the reaction o...

Activated macrophages and granulocytes lyse tumor cells in the presence of phorbol myristate acetate or antitumor antibody via the secretion of reactive oxygen intermediates, such as HzOz. We compared the lysis of GSH-depleted or normal tumor cells by oxidants generated with glucose oxidase or activated macrophages and granulocytes. Two independent methods were employed to deplete cells specifi...

Apoptosis is characterized by the activation of specific biochemical pathways that lead to the organized demise of cells. Intracellular GSH depletion has been observed during apoptosis; however, neither the mechanisms involved in the reduction of the intracellular GSH concentration, [GSH](i), nor its link to the progression of apoptosis have been elucidated. We have studied this issue using Fas...

The role of organic anion transporters in the mitochondrial uptake of glutathione (GSH) was investigated by assessing competition with substrates or inhibition with inhibitors of specific carriers and modulation of mitochondrial energetics. Potential artifacts in the transport methodology, including contamination of matrix space with extramitochondrial fluid, changes in matrix volume during inc...

The antioxidant activity of flavonoids, directly through scavenging oxidizing species and indirectly through modulating drug-metabolizing enzyme activities, is associated with chemopreventive and chemotherapeutic effects. However, little published information is available concerning the effect of flavonoids on glutathione (GSH) homeostasis. We previously demonstrated that PD98059 (2'-amino-3'-m...

Despite reports of lower GSH concentration in sickle cell disease (SCD), the in vivo kinetic mechanism(s) responsible for GSH deficiency is unknown. To determine whether suppressed synthesis was responsible for the lower erythrocyte GSH concentration, we used a primed intermittent infusion of [(2)H(2)]glycine to measure erythrocyte GSH synthesis in vivo in 23 individuals with homozygous beta(s)...

The integrity of the vascular endothelium of the blood-brain barrier (BBB) is central to cerebrovascular homeostasis. Given the function of the BBB as a physical and metabolic barrier that buffers the systemic environment, oxidative damage to the endothelial monolayer will have significant deleterious impact on the metabolic, immunological, and neurological functions of the brain. Glutathione (...

We have previously demonstrated that resveratrol (Resv)-induced cellular apoptosis occurs after formation of reactive oxygen species (ROS) but the role of GSH has not been well defined. Our experimental data enumerated that Resv treatment (50 μm) induced apoptosis in human leukemic monocyte lymphoma cells, which was preceded by cellular GSH efflux. High concentration of extracellular thiol (GSH...

Both glutathione (γ-glutamylcysteinylglycine; GSH) and the metalloprotein metallothionein (MT) are composed of approximately one-third cysteine. Both have antioxidant activity and are induced by oxidant stresses and heavy metals. Intracellular cysteine levels may depend on uptake and reduction of extracellular cystine. GSH synthesis can be limited by the activity of the [Formula: see text] cyst...