[59] Glutathione disulfide (GSSG) efflux from cells and tissues

Sies, Helmut; Akerboom, Theodorus P.M.

doi:10.1016/s0076-6879(84)05062-x

Cited by 192 publications

(96 citation statements)

References 27 publications

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“…Blood GSH and GSSG levels were determined by the 5,5-dithio-bis (2-nitrobenzoic acid) (DTNB) assay according to the previous reported method 27 with a minor modification. Briefly, whole blood was kept in cold metaphosphoric acid (5%) buffer after the blood draw.…”

Section: Determination Of Glutathione Levelsmentioning

confidence: 99%

Subfertility and growth restriction in a new galactose-1 phosphate uridylyltransferase (GALT) - deficient mouse model

et al. 2014

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The first GalT gene knockout (KO) mouse model for Classic Galactosemia (OMIM 230400) accumulated some galactose and its metabolites upon galactose challenge, but was seemingly fertile and symptom free. Here we constructed a new GalT genetrapped mouse model by injecting GalT gene-trapped mouse embryonic stem cells into blastocysts, which were later implanted into pseudo-pregnant females. High percentage GalT gene-trapped chimera obtained were used to generate heterozygous and subsequently, homozygous GalT gene-trapped mice. Biochemical assays confirmed total absence of galactose-1 phosphate uridylyltransferase (GALT) activity in the homozygotes. Although the homozygous GalT gene-trapped females could conceive and give birth when fed with normal chow, they had smaller litter size (P ¼ 0.02) and longer time-to-pregnancy (P ¼ 0.013) than their wild-type littermates. Follicle-stimulating hormone levels of the mutant female mice were not significantly different from the age-matched, wild-type females, but histological examination of the ovaries revealed fewer follicles in the homozygous mutants (P ¼ 0.007). Administration of a high-galactose (40% w/w) diet to lactating homozygous GalT gene-trapped females led to lethality in over 70% of the homozygous GalT gene-trapped pups before weaning. Cerebral edema, abnormal changes in the Purkinje and the outer granular cell layers of the cerebellum, as well as lower blood GSH/GSSG ratio were identified in the galactose-intoxicated pups. Finally, reduced growth was observed in GalT gene-trapped pups fed with normal chow and all pups fed with high-galactose (20% w/w) diet. This new mouse model presents several of the complications of Classic Galactosemia and will be useful to investigate pathogenesis and new therapies.

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Section: Determination Of Glutathione Levelsmentioning

confidence: 99%

Subfertility and growth restriction in a new galactose-1 phosphate uridylyltransferase (GALT) - deficient mouse model

et al. 2014

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“…Livers from male Wistar rats (120-250 g body mass), either 24-h-starved or fed adlibitum on a stock diet (Altromin), were perfused as described previously [19] in a non-recirculating manner with bicarbonate-buffered Krebs-Henseleit saline plus L-lactate (2.1 mmol t 1-'), pyruvate (0.3 mmol.l-') and leucine (0.1 mmol . 1-').…”

Section: Liver Perfusionmentioning

confidence: 99%

Control of hepatic proteolysis by amino acids

Hallbrucker

Dahl

Läng

et al. 1991

European Journal of Biochemistry

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1. Proteolysis in isolated perfused rat liver was monitored as [3H]leucine release into effluent perfusate after in vivo labeling by intraperitoneal injection of [3H]leucine about 16 h prior to the perfusion experiment. Exposure of the livers to hypotonic perfusion media (175 -295 mOsmol . 1-I) increased liver mass due to cell swelling and inhibited [3H]leucine release. The extent of inhibition of [3H]leucine release was linearly related to the liver-mass increase, regardless of whether livers from fed or 24-h-starved rats were studied.2. Infusion of glycine (0.5-3 mmol . 1-I) or glutamine (0.5-3 mmol . 1-') during normotonic perfusions (305 mOsmol . 1-') led to a concentration-dependent increase of liver mass and inhibition of [3H]leucine release. The inhibition of [3H]leucine release was again strongly dependent upon the increase of liver mass, regardless of whether cell swelling was induced by glutamine or glycine in normotonic perfusions, by exposure of the liver to hypotonic media or whether amino-acid-induced cell swelling was modified by the nutritional state. The effects of glutamine and glycine on [3H]leucine release were additive to the same extent as that found when the liver-mass increase was observed.3. Alanine, serine and proline inhibited [3H]leucine release in parallel to the extent of amino-acid-induced liver-mass increase; however, the inhibition of [3H]leucine release was about twice that found when comparable degrees of cell swelling were induced either by hypotonic exposure or by addition of glutamine or glycine. The relationship between alanine-induced liver-mass increase and the inhibition of [3H]leucine release was also maintained in presence of aminooxyacetate (0.2 mmol . 1-I).4. Infusion of an amino acid mixture, roughly mimicking the concentrations found in portal venous blood, to livers from 24-h-starved or fed rats inhibited [3H]leucine release by 56.0 & 2.4% (n = 6) or 31.1 f 2.3% (n = 3), respectively, and increased liver mass by 5.0 & 0.1 YO (n = 6) or 2.2 f 0.3% (n = 3), respectively. Regardless of the nutritional state, there was a close relationship between the amino-acid-mixture-induced (and also phenylalanineinduced) increase of liver mass and the degree of inhibition of [3H]leucine release; however, the inhibition of [3H]leucine release was about fourfold higher than that found when comparable degrees of cell swelling were induced by hypotonic exposure. The amino-acid-mixture-induced inhibition of [3H]leucine release was reversed by hypertonic (385 mOsmol . 1-I) cell shrinkage and stimulated by glutamine/glycine-induced swelling to an cxtcnt predicted by the relationship between liver mass and anisotonic cell swelling.5. The data are consistent with the following: (a) a role of liver-cell volume in the control of hepatic proteolysis; (b) inhibition of proteolysis by glutamine and glycine can largely be ascribed to cell-volume changes, whereas the effects of alanine, serine, proline and especially of phenylalanine or of an amino acid mixture on proteolysis can only be explain...

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“…Livers of male Wistar rats of 100 -200 g body weight, fed ad libitum on stock diet (Altromin), were perfused in situ or isolated as described previously [30] without recirculation of the perfusate using the bicarbonate-buffered Krebs-Henseleit saline plus L-lactate (2.1 mM) and pyruvate (0.3 mM). When indicated the Ca2 + concentration in the perfusate was lowered from 1.25 mM to 0.3 mM.…”

Section: Hemoglobin-free Liver Perfusionmentioning

confidence: 99%

Hepatocyte heterogeneity in response to extracellular ATP

Häussinger

Stehlé

Gerok

et al. 1987

European Journal of Biochemistry

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1. The metabolic and hemodynamic effects of extracellular ATP in perfused rat liver were compared during physiologically antegrade (portal to hepatic vein) and retrograde (hepatic to portal vein) perfusion. ATP in concentrations up to 100 pM was completely hydrolyzed during a single liver passage regardless of the perfusion direction.2. The ATP(20 pM)-induced increases of glucose output, perfusion pressure and ammonium ion release seen during antegrade perfusions were diminished by 85 -95% when the perfusion was in the retrograde direction, whereas the amount of Ca2+ mobilized from the liver was decreased by only 60%. The maximal rate of initial K + uptake following ATP was dependent on the amount of Ca2+ mobilized regardless of the direction of perfusion. In the presence of UMP (1 mM), an inhibitor of ATP hydrolysis by membrane-bound nucleotide pyrophosphatase, the effect of the direction of perfusion on the glycogenolytic response to ATP (20 pM) was largely diminished.3. For a maximal response of glucose output, Ca2+ release and perfusion pressure to extracellular ATP, concentrations of about 20 pM, 50 pM and 100 pM were required during antegrade perfusion, respectively. These maximal responses could also be obtained during retrograde perfusion, but higher ATP concentrations were required (120 pM, 80 pM, above 200 pM, respectively).4. 14C02 production from [I -14C]glutamate which occurs predominantly in the perivenous hepatocytes capable of glutamine synthesis was stimulated by extracellular ATP (20 pM); it was only slightly affected by the direction of perfusion. In antegrade perfusions, ATP (20 pM) increased I4CO2 production from 88 to 162 nmol g-lmin-', compared to an increase from 91 to 148 nmol g-' min-' in retrograde perfusion.5. The data are interpreted to suggest that (a) extracellular ATP is predominantly hydrolyzed by a small hepatocyte population located at the perivenous outflow of the acinus; (b) glycogenolysis to glucose is predominantly localized in the periportal area; (c) contractile elements (sphincters) exist near the inflow of the sinusoidal bed; (d) a considerable portion of the Ca2+ mobilized by ATP is derived from liver cells that do not contribute to hepatic glucose output.In liver, extracellular ATP (for review see [l]) stimulates glycogenolysis [2-61 and citric acid cycle flux [7], increases the portal pressure [S, 61, induces K+ [6,[9][10][11] and Ca2+ fluxes [5, 6, 81 diacylglycerol following an activation of the P,-purinergic receptor [18 -211. Besides ATP and ADP, other extracellular nucleoside phosphates, such as UTP and UDP are also potential regulators of hepatic metabolism or microcirculation. Interestingly, ATP leads to responses qualitatively and quantitatively different from those observed with UTP and there is some indication that both nucleotides may act on different receptors [6]. Extracellular ATP and other purine and pyrimidine nucleotides are hydrolyzed by isolated hepatocytes and livers in vitro and in vivo [Il, 22, 231. Among the enzymes involved in ATP hydrolysis...

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[59] Glutathione disulfide (GSSG) efflux from cells and tissues

Cited by 192 publications

References 27 publications

Subfertility and growth restriction in a new galactose-1 phosphate uridylyltransferase (GALT) - deficient mouse model

Subfertility and growth restriction in a new galactose-1 phosphate uridylyltransferase (GALT) - deficient mouse model

Control of hepatic proteolysis by amino acids

Hepatocyte heterogeneity in response to extracellular ATP

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