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

Ookhtens, Murad; Kaplowitz, Neil

doi:10.1055/s-2007-1007167

Cited by 176 publications

(142 citation statements)

References 2 publications

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“…[13] In addition to serving as a strate for glutathione related enzymes, GSH acts as a free radical scavenger, a generator of a α-tocopherol and plays an important role in the maintenance of protein sulfhydryl groups. [14] In the present study, the levels of GSH were decreased significantly in high fat diet ingestion indicating the oxidative stress. GPx has a well-established role in protecting cells against oxidative injury.…”

Section: Resultssupporting

confidence: 54%

In vivo anti-oxidant activity of Dhatrinisha churna and Manjisthadi churna in high fat diet induced oxidative stress

Vishal¹,

Rakesh

2012

Free Radicals and Antioxidants

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Section: Resultssupporting

confidence: 54%

In vivo anti-oxidant activity of Dhatrinisha churna and Manjisthadi churna in high fat diet induced oxidative stress

Vishal¹,

Rakesh

2012

Free Radicals and Antioxidants

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“…16 There are a number of pitfalls in measurement but 3 modern methods are in fairly close agreement that concentrations of plasma GSH are about 20 µmol/L 16 and that hepatic vein concentrations are higher at about 30 µmol/L. 16 This is within the range of concentration for which the authors have demonstrated inhibitory activity of GSH for MMP9. Using in situ microdialysis, Yang et al measured basal extracellular GSH concentrations in the livers of anesthetized rats.…”

Section: Discussionmentioning

confidence: 94%

“…18 However, the exact role of extracellular glutathione remains poorly understood. 16 Glutathione is also a heavy metal-binding ligand, binding to mercury, copper, zinc, and other metals of biological importance, via the sulfhydryl group of the cysteine moiety. 19 As such, it is one of a group of thiols, such as N-acetylcysteine, dithioerythritol, and 2-mercaptoethanol that have been used to inhibit metalloproteinases in a variety of experimental situations.…”

Section: Discussionmentioning

confidence: 99%

Glutathione, lactobionate, and histidine: cryptic inhibitors of matrix metalloproteinases contained in university of wisconsin and histidine/tryptophan/ketoglutarate liver preservation solutions

Upadhya

Strasberg

2000

Hepatology

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UW solution and HTK solution are both used for cold preservation of liver allografts. Although they are about equally effective, their compositions are very different, and they were formulated using different rationales. The authors recently showed an important role for MMPs in liver preservation injury and consequently postulated that these preservation solutions contain cryptic inhibitors of MMP activity. To determine this possibility, the ability of these solutions to inhibit MMP activity was studied. The source of MMP2 and MMP9 was human liver effluents obtained at the time of liver transplantation or commercially available human recombinant MMP2 and MMP9. MMP2 and MMP9 showed gelatinolytic activity at 37ЊC and also at 4ЊC, although activity at 4ЊC was reduced. Activity was inhibited by University of Wisconsin (UW) and Histidine/Tryptophan/ Ketoglutarate (HTK) solutions. Examination of individual ingredients disclosed that reduced glutathione (GSH) and lactobionate in UW solution and histidine in HTK solution were the cryptic inhibitors. HTK solution was a more effective inhibitor than UW solution. GSH inhibited the activity of both enzymes, but was a much more effective inhibitor of MMP9 than MMP2. Oxidized glutathione(GSSG) was a much less effective inhibitor of the enzymes. The inhibitor constants (K i ) of GSH for MMP2 and MMP9 were 34 mol/L and 3 mol/L, respectively. The authors conclude that MMP inhibition is a cryptic property of both commonly used liver preservation solutions and contributes importantly to their action. Furthermore, GSH appears to be an effective inhibitor of gelatinases at concentrations at which it is normally present in extracellular fluid. (HEPATOLOGY 2000;31:1115-1122.)University of Wisconsin (UW) solution became the standard liver preservation solution more than 10 years ago. 1,2 It greatly improved the results of hepatic preservation compared with Eurocollins solution, which was in common use before that time. 1,2 UW solution was formulated with specific ingredients to retard the 4 classical effects of hypothermiacell swelling, impaired energy metabolism, acidosis, and accumulation of precursors of reactive oxygen intermediates. 2 Metalloproteinase inhibition was not a goal of its formulation because the role of metalloproteinases in preservation injury 3 was unknown at the time that UW solution was devised.Bretschneider' s solution, also known as histidine/tryptophan/ketoglutarate solution, or HTK solution 4 is also used for liver preservation, mainly in Germany. HTK solution was originally introduced as a cardioplegic solution and was later adapted to cold preservation of organs. It was formulated to retard acidosis (histidine), to prevent membrane injury (tryptophan), and to provide a substrate for energy metabolism (ketoglutarate). Like UW solution, inhibition of metalloproteinases was not a goal of its formulation.Two recent human studies, 5,6 one of which was a randomized controlled trial, 6 compared effectiveness of UW and HTK solutions. These studies found that the sol...

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“…Transport of these amino acids is accomplished by well-characterized amino acid transporters (13,14). More recently, distinct transport systems for GSH have been described on the canalicular and sinusoidal membranes of rat and human liver, and analysis of cell lines and tissues suggests that a transport mechanism also exists on certain other cell types (15)(16)(17)(18).…”

mentioning

confidence: 99%

The Phagocytosis-Associated Respiratory Burst in Human Monocytes Is Associated with Increased Uptake of Glutathione

Seres

Knickelbein

Warshaw

et al. 2000

The Journal of Immunology

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During the phagocytic respiratory burst, oxygen is converted to potent cytotoxic oxidants. Monocytes and macrophages are potentially long-lived, and we have hypothesized that protective mechanisms against oxidant stress are varied and fully expressed in these cells. We report here that the respiratory burst in monocytes is accompanied by an increase in the uptake of [35S]glutathione ([35S]GSH) after 20–30 min to levels up to 10-fold greater than those at baseline. By 30 min, 49% of the cell-associated radioactivity was in the cytosol, 41% was in membrane, and 10% was associated with the nuclear fraction. GSH uptake was inhibited by catalase, which removes hydrogen peroxide (H2O2), and micromolar H2O2 stimulated GSH uptake effectively in monocytes and also lymphocytes. Oxidation of GSH to glutathione disulfide with H2O2 and glutathione peroxidase prevented uptake. Acivicin, which inhibits GSH breakdown by γ-glutamyl transpeptidase (GGT), had no effect on the enhanced uptake seen during the respiratory burst. Uptake of cysteine or cystine, possible products of GGT activity, stayed the same or decreased during the respiratory burst. These results suggest that a GGT-independent mechanism is responsible for the enhanced GSH uptake seen during the respiratory burst. We describe here a sodium-independent, methionine-inhibitable transport system with a Km (8.5 μM) for GSH approximating the plasma GSH concentration. These results suggest that monocytes have a specific GSH transporter that is triggered by the release of H2O2 during the respiratory burst and that induces the uptake of GSH into the cell. Such a mechanism has the potential to protect the phagocyte against oxidant damage.

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

Cited by 176 publications

References 2 publications

In vivo anti-oxidant activity of Dhatrinisha churna and Manjisthadi churna in high fat diet induced oxidative stress

In vivo anti-oxidant activity of Dhatrinisha churna and Manjisthadi churna in high fat diet induced oxidative stress

Glutathione, lactobionate, and histidine: cryptic inhibitors of matrix metalloproteinases contained in university of wisconsin and histidine/tryptophan/ketoglutarate liver preservation solutions

The Phagocytosis-Associated Respiratory Burst in Human Monocytes Is Associated with Increased Uptake of Glutathione

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