Glutathione homeostasis is disturbed in CD4‐positive lymphocytes of HIV‐seropositive individuals

Ven, A.J.A.M. van der; Blom, Henk J.; Peters, W.H.M.; Jacobs, L.; Verver-Jansen, T.J.G.; Koopmans, P.P.; Demacker, P.N.M.; Meer, J.W.M. van der

doi:10.1046/j.1365-2362.1998.00267.x

Cited by 35 publications

(17 citation statements)

References 31 publications

(54 reference statements)

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“…Examples of such studies are those by Aukrust et a]., 123 Lopez Galera et al,l*"nd van der Ven et a1. 125 The first group123 has found only mild decreases in plasma levels of total glutathione (-20%, statistically not significant) and GSSG (-30%) and slight (-10%) decreases in plasma CYSS levels in seropositive subjects compared with healthy controls.l2' Thus, they failed to observe the marked cyst(e)ine deficiency reported by others. Moreover, they found no significant differences in plasma levels of glutathione and cyst(e)ine moieties between asymptomatic and symptomatic subjects.…”

Section: Correlates Of Glutathione Homeostasis and Various Diseasesmentioning

confidence: 89%

Role of the Liver in Interorgan Homeostasis of Glutathione and Cyst(e)ine

Ookhtens¹,

Kaplowitz²

1998

Semin Liver Dis

181

131

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The most widely recognized function of reduced glutathione (GSH) is its defense against toxic compounds, whether exogenous, such as electophilic xenobiotics, or endogenous, such as reactive oxygen species, generated during normal oxidative metabolism and/or stress. However another no less significant role of GSH-namely its function as a reservoir and vehicle for packaging and transport of cyst(e)ine-has been receiving increasing attention. Because GSH is relatively more auto-oxidation resistant and stable than cyst(e)ine (CYSH), it serves as the preferred form for storage and transport of the latter especially in the extracellular and relatively much less reduced (than intracellular) milieu, where CYSH oxidizes to cystine (CYSS) rapidly. Over the past two decades, significant work has been going on to delineate the intra- and extrahepatic (interorgan) turnover, transport, and disposal of GSH and define the quantitative role of these processes in interorgan homeostasis of GSH, CYSH, and CYSS. These studies have identified the liver as the central organ of interorgan GSH homeostasis, with sinusoidal GSH efflux as the major determinant of plasma GSH, CYSH, CYSS, and thiol-disulfide status of plasma. This article focuses on the principal components and determinants of interorgan homeostasis of GSH and its breakdown products. It also presents the current state of knowledge under both normal and diseased states.

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Section: Correlates Of Glutathione Homeostasis and Various Diseasesmentioning

confidence: 89%

Role of the Liver in Interorgan Homeostasis of Glutathione and Cyst(e)ine

Ookhtens¹,

Kaplowitz²

1998

Semin Liver Dis

181

131

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show abstract

“…Intracellular sulfhydryls other than GSH can potentially bind monochlorobimane and generate fluorescent adducts [ 59]. However, GSB values in individual T cell subsets obtained by monochlorobimane staining under our conditions primarily report reduced intracellular GSH since GSB values for CD4 T cells (and other lymphocytes) correlate with HPLC‐measured GSH in whole blood ( r = 0.64, P < 0.0001) [ 46].…”

Section: Methodsmentioning

confidence: 99%

N‐acetylcysteine replenishes glutathione in HIV infection

Rosa

Zaretsky

Dubs

et al. 2000

Eur J Clin Investigation

258

176

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NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.

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“…Plasma GSH concentrations are known to decline with age (132), and low plasma GSH is associated with a variety of diseases or conditions, including myocardial dysfunction (133), early atherosclerosis (134), neurodegenerative diseases (135), and HIV infection (136). Higher levels of GSH are commonly assumed to represent a healthier redox environment (93,134).…”

Section: Gsh Clinicial and Mechanistic Considerationsmentioning

confidence: 99%

A nutrient‐dense, high‐fiber, fruit‐based supplement bar increases HDL cholesterol, particularly large HDL, lowers homocysteine, and raises glutathione in a 2‐wk trial

Mietus‐Snyder¹,

Shigenaga²,

Suh³

et al. 2012

FASEB j.

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Dietary intake modulates disease risk, but little is known how components within food mixtures affect pathophysiology. A low-calorie, high-fiber, fruit-based nutrient-dense bar of defined composition (e.g., vitamins and minerals, fruit polyphenolics, β-glucan, docosahexaenoic acid) appropriate for deconstruction and mechanistic studies is described and evaluated in a pilot trial. The bar was developed in collaboration with the U.S. Department of Agriculture. Changes in cardiovascular disease and diabetes risk biomarkers were measured after 2 wk twice-daily consumption of the bar, and compared against baseline controls in 25 healthy adults. Plasma HDL-cholesterol (HDL-c) increased 6.2% (P=0.001), due primarily to a 28% increase in large HDL (HDL-L; P<0.0001). Total plasma homocysteine (Hcy) decreased 19% (P=0.017), and glutathione (GSH) increased 20% (P=0.011). The changes in HDL and Hcy are in the direction associated with decreased risk of cardiovascular disease and cognitive decline; increased GSH reflects improved antioxidant defense. Changes in biomarkers linked to insulin resistance and inflammation were not observed. A defined food-based supplement can, within 2 wk, positively impact metabolic biomarkers linked to disease risk. These results lay the groundwork for mechanistic/deconstruction experiments to identify critical bar components and putative synergistic combinations responsible for observed effects.

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Glutathione homeostasis is disturbed in CD4‐positive lymphocytes of HIV‐seropositive individuals

Abstract: We conclude that the glutathione homeostasis is disturbed in CD4+ lymphocytes of HIV-seropositive individuals. The glutathione redox dysbalance in CD4+ lymphocytes could be important in the pathogenesis of HIV infection and have implications for therapy.

Cited by 35 publications

References 31 publications

Role of the Liver in Interorgan Homeostasis of Glutathione and Cyst(e)ine

Role of the Liver in Interorgan Homeostasis of Glutathione and Cyst(e)ine

N‐acetylcysteine replenishes glutathione in HIV infection

A nutrient‐dense, high‐fiber, fruit‐based supplement bar increases HDL cholesterol, particularly large HDL, lowers homocysteine, and raises glutathione in a 2‐wk trial

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