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- Hultberg, Malin, et al.
(författare)
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Glutathione turnover in human cell lines in the presence of agents with glutathione influencing potential with and without acivicin inhibition of gamma-glutamyltranspeptidase.
- 2005
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Ingår i: Biochimica et Biophysica Acta. General Subjects. - : Elsevier BV. - 0304-4165. ; 1726:1, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously shown that there were great discrepancies between different agents regarding their glutathione stimulating potential and that agents with mainly oxidative effects did not increase concentrations of glutathione in human cell cultures, in contrast to other thiol reactive agents. In order to evaluate whether increased glutathione degradation might be one reason for these discrepancies, we have investigated the effect of different agents with potential influence on glutathione metabolism in human cell cultures with or without acivicin inhibition of gamma-glutamyltranspeptidase (GT), since GT is responsible for the initial degradation of glutathione. Methods: Intra- and extracellular concentrations of glutathione were investigated in HeLa and hepatoma cell cultures, with and without acivicin inhibition of GT, in the presence of oxidative and electrophilic agents (copper ions, hydrogen peroxide and N-ethylmaleimide), hydroquitione, reducing agents (lipoic acid and N-acetylcysteine), and a thiol reactive metal (mercury ions). Results: There were great discrepancies between the different agents regarding their maximal glutathione response (the sum of the intracellular and the extracellular amount of glutathione) in cell cultures. There was only a small increase in total glutathione in the presence of hydrogen peroxide or N-ethylmaleimide before the cell protein decreased compared to findings with mercury ions, lipoic acid or hydroquinone. In both HeLa and hepatoma cell cultures, there were correlations between the original glutathione amount and the total glutathione amount observed after acivicin inhibition. Conclusion: The relatively small increase of glutathione amount in the presence of oxidative and electrophilic agents compared to other thiol reactive agents is not due to increased GT degradation of glutathione.
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| 2. |
- Hultberg, Malin, et al.
(författare)
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Oxidative stress decreases extracellular homocysteine concentration in human hepatoma (HepG2) cell cultures
- 2007
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Ingår i: Chemico-Biological Interactions. - : Elsevier BV. - 1872-7786 .- 0009-2797. ; 165:1, s. 54-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mild hyperhomocysteinemia is associated with premature vascular disease. The mechanism behind the vascular injuries is, however, still unknown. Homocysteine may be catabolized in the trans sulfuration pathway to cysteine. Cystathionine beta-synthase, which catalyses the first step in the transsulfuration pathway is redox-sensitive. We have therefore investigated total extracellular homocysteine turnover in the presence of oxidative stress in human cell lines. Methods: The turnover of total extracellular homocysteine in HeLa and hepatoma cell cultures has been investigated in the presence of hydrogen peroxide. Furthermore, the effect of hydrogen peroxide on the removal of high amounts of exogenously added homocysteine was also studied. Results: Total extracellular homocysteine concentration in hepatoma cell cultures decreased in the presence of hydrogen peroxide, whereas the extracellular homocysteine concentration in HeLa cell cultures was not influenced. There was no significant change of intracellular homocysteine in any type of cell cultures. Furthermore, the presence of hydrogen peroxide did not increase the removal of exogenously added homocysteine. Conclusion: The presence of hydrogen peroxide probably increases the activity of the transsulfuration pathway in hepatoma cell cultures, which increases the intracellular use of homocysteine and lowers its extracellular release. Consequently this mechanism might tend to lower total plasma homocysteine concentration in oxidative stress. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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| 4. |
- Hultberg, Malin, et al.
(författare)
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The polyphenol quercetin strongly increases homocysteine production in a human hepatoma (Hep G2) cell line.
- 2006
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 39:2, s. 160-163
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The metabolism of homocysteine is influenced by several dietary factors, including folate, cobalamin and possibly also the intake of polyhydroxylated phenolic compounds (polyphenols), which were shown to increase plasma homocysteine (tHcy) concentration. In order to reveal the cause of the increased plasma tHcy, we have therefore investigated the effects of a polyphenol in cell cultures from human cell lines. Design and methods: We have studied the influence of the polyphenol quercetin (Quer) on intra- and extracellular homocysteine concentrations in HeLa and hepatoma cell cultures. Results: The main finding is an increased concentration of extracellular homocysteine in the presence of Quer in hepatoma cell cultures, whereas there were no significant changes of homocysteine concentration in HeLa cell cultures. There was no effect on cellular growth, as judged by cell protein. The presence of adenosyl-dialdehyde, an inhibitor of adenosyl-homocysteine hydrolase, abolished the increased extracellular concentration of homocysteine observed in hepatoma cell cultures in the presence of Quer. Conclusion: The antioxidative agent Quer strongly increased the extracellular concentration of homocysteine in hepatoma cell cultures probably due to increased cellular methylation. In the human body, the same phenomenon might lead to increased plasma tHcy. Since elevated plasma tHcy is associated with premature vascular disease, high long-lasting dietary intake of polyphenols might be harmful. The interaction between Quer and homocysteine turnover may therefore warrant a re-evaluation of polyphenols as relatively harmless antioxidative food supplements or therapeutic antioxidative agents. (c) 2005 The Canadian Society of Clinical Chemists. All rights reserved.
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| 5. |
- Hultberg, Malin, et al.
(författare)
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Traces of copper ions deplete glutathione in human hepatoma cell cultures with low cysteine content
- 2007
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Ingår i: Chemico-Biological Interactions. - : Elsevier BV. - 1872-7786 .- 0009-2797. ; 167:1, s. 56-62
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cell death induced by intracellutar glutathione depletion has been reported to be dependent on the presence of trace amounts of extracellular copper ions. Since little is known about the relationship between glutathione depletion and copper homeostasis, we have in the present study further investigated the role of low amounts of copper ions in glutathione depletion. Methods: Glutathione turnover was investigated in HeLa and hepatoma cell cultures with normal and low cysteine content in the presence of copper ions (1 and 10 mu mol/L) and two other glutathione-stimulating agents (lipoic acid and mercury ions). Results: Copper ions (10 mu mol/L) caused relatively small increases in total amount of glutathione (the sum of the intracellular and the extracellular amount of glutathione) in HeLa and hepatoma cell cultures with normal cysteine levels (420 nmol/mL) compared to control cell cultures, whereas lipoic acid and mercury ions strongly increased total glutathione in both types of cell cultures. Lower amount of total glutathione was observed in cell cultures with a lower cysteine levels (84 nmol/mL), which is similar to that in human plasma. A strongly decreased total amount of glutathione in the presence of copper ions was observed in hepatoma cell cultures with lower cysteine levels, whereas the other agents showed effects similar to those described for cell cultures with normal cysteine levels. Conclusion: Glutathione synthesis in hepatoma cell cultures is probably more sensitive to a low cysteine level than HeLa cell cultures, and the presence of copper ions further decreases the availability of cysteine probably by increasing the disultide binding to cysteine residues in extracellular proteins, which causes a further decrease of total glutathione. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
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| 9. |
- Hallert, Claes, 1945-, et al.
(författare)
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B vitamins improve health in patients with coeliac disease living on a gluten-free diet
- 2009
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 29:8, s. 811-816
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with coeliac disease living on a gluten-free diet show vitamin deficiency and reduced subjective health status. Aim To study the biochemical and clinical effects of B vitamin supplementation in adults with longstanding coeliac disease. Methods In a double blind placebo controlled multicentre trial, 65 coeliac patients (61% women) aged 45–64 years on a strict gluten-free diet for several years were randomized to a daily dose of 0.8 mg folic acid,0.5 mg cyanocobalamin and 3 mg pyridoxine or placebo for 6 months. The outcome measures were psychological general well-being (PGWB) and the plasma total homocysteine (tHcy) level, marker of B vitamin status. Results Fifty-seven patients (88%) completed the trial. The tHcy level was baseline median 11.7 μmol/L (7.4–23.0), significantly higher than in matched population controls [10.2 μmol/L (6.7–22.6) (P < 0.01)]. Following vitamin supplementation, tHcy dropped a median of 34% (P < 0.001), accompanied by significant improvement in well-being (P < 0.01), notably Anxiety (P < 0.05) and Depressed Mood (P < 0.05) for patients with poor well-being. Conclusions Adults with longstanding coeliac disease taking extra B vitamins for 6 months showed normalized tHcy and significant improvement in general well-being, suggesting that B vitamins should be considered in people advised to follow a gluten-free diet.
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