Glutathione transport system in human small intestine epithelial cells

Iantomasi, Teresa; Favilli, Franco; Marraccini, Patrizia; Magaldi, Thomas G.; Bruni, Paola; Vincenzini, Massimo

doi:10.1016/s0005-2736(97)00097-7

Cited by 65 publications

(32 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although biochemical evidence for GSH uptake has been reported for gram-positive bacteria (59), yeasts (44), plants (22), and mammalian cells (31), the import of GSX from the growth medium as the exclusive source of GSH for H. influenzae NCTC 8143 cells reported here is rather surprising because H. influenzae belongs to the aerobic gram-negative bacteria which are thought to endogenously synthesize the thiol tripeptide (15). While the uptake of GSX appears to be redundant under standard laboratory conditions for log-phase H. influenzae NCTC 8143 growing in complex medium, GSH accumulation is essential for growth in minimal broth lacking cysteine, indicating that GSH can be catabolized to meet the requirement of H. influenzae NCTC 8143 for cysteine.…”

Section: Discussionmentioning

confidence: 99%

Exogenous Glutathione Completes the Defense against Oxidative Stress in Haemophilus influenzae

et al. 2003

View full text Add to dashboard Cite

Since they are equipped with several strategies by which they evade the antimicrobial defense of host macrophages, it is surprising that members of the genus Haemophilus appear to be deficient in common antioxidant systems that are well established to protect prokaryotes against oxidative stress. Among others, no genetic evidence for glutathione (␥-Glu-Cys-Gly) (GSH) biosynthesis or for alkyl hydroperoxide reduction (e.g., the Ahp system characteristic or enteric bacteria) is apparent from the Haemophilus influenzae Rd genome sequence, suggesting that the organism relies on alternative systems to maintain redox homeostasis or to reduce small alkyl hydroperoxides. In this report we address this apparent paradox for the nontypeable H. influenzae type strain NCTC 8143. Instead of biosynthesis, we could show that this strain acquires GSH by importing the thiol tripeptide from the growth medium. Although such GSH accumulation had no effect on growth rates, the presence of cellular GSH protected against methylglyoxal, tert-butyl hydroperoxide (tBuOOH), and S-nitrosoglutathione toxicity and regulated the activity of certain antioxidant enzymes. H. influenzae NCTC 8143 extracts were shown to contain GSH-dependent peroxidase activity with t-BuOOH as the peroxide substrate. The GSH-mediated protection against t-BuOOH stress is most probably catalyzed by the product of open reading frame HI0572 (Prx/Grx), which we isolated from a genomic DNA fragment that confers wild-type resistance to t-BuOOH toxicity in the Ahp-negative Escherichia coli strain TA4315 and that introduces GSH-dependent alkyl hydroperoxide reductase activity into naturally GSH peroxidase-negative E. coli. Finally, we demonstrated that cysteine is an essential amino acid for growth and that cystine, GSH, glutathione amide, and cysteinylglycine can be catabolized in order to complement cysteine deficiency.

show abstract

Section: Discussionmentioning

confidence: 99%

Exogenous Glutathione Completes the Defense against Oxidative Stress in Haemophilus influenzae

et al. 2003

View full text Add to dashboard Cite

show abstract

“…It is likely that this membrane transport system causes GSH to efflux to the lung ELF. The function of such a GSH transport system is influenced by the redox/thiol status of the cell, the membrane potential and presence of cations in the extracellular environment [138,139]. GSH-related structural compounds, such as glutathione-S-conjugates and GSH ethyl ester, inhibit cellular GSH uptake or influx [137,138].…”

Section: Role Of C-glutamyl Transpeptidase In the Regulation Of Glutamentioning

confidence: 99%

“…The function of such a GSH transport system is influenced by the redox/thiol status of the cell, the membrane potential and presence of cations in the extracellular environment [138,139]. GSH-related structural compounds, such as glutathione-S-conjugates and GSH ethyl ester, inhibit cellular GSH uptake or influx [137,138]. Furthermore, a more oxidized extracellular environment stimulates cells to retain GSH, whereas a more reduced extracellular state facilitates GSH efflux [137,140].…”

Section: Role Of C-glutamyl Transpeptidase In the Regulation Of Glutamentioning

confidence: 99%

“…Epithelial cells also take up glutathione by a redox-dependent mechanism [137]. This transport system may act to regulate intracellular glutathione depending on the presence of reduced thiols or disulphides in the extracellular environment [138]. Thus, the short-term effects of various oxidants and oxidant-generating systems appear to be to upregulate the gene for glutathione synthesis, possibly providing a protective/adaptive mechanism against subsequent oxidative stress (table 2).…”

Section: Effects Of Oxidantsmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative stress and regulation of glutathione in lung inflammation

Rahman¹,

MacNee²

2000

Eur Respir J

802

549

View full text Add to dashboard Cite

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance, a major cause of cell damage. The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox‐sensitive transcription factors such as nuclear factor‐κB, and activator protein‐1 (AP‐1), which regulate the genes for pro‐inflammatory mediators and protective antioxidant genes. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra‐ and extracellular protective antioxidant against oxidative/nitrosative stresses, which plays a key role in the control of pro‐inflammatory processes in the lungs. Recent findings have suggested that GSH is important in immune modulation, remodelling of the extracellular matrix, apoptosis and mitochondrial respiration. The rate‐limiting enzyme in GSH synthesis is γ‐glutamylcysteine synthetase (γ‐GCS). The human γ‐GCS heavy and light subunits are regulated by AP‐1 and antioxidant response elements and are modulated by oxidants, phenolic antioxidants, growth factors, and inflammatory and anti‐inflammatory agents in lung cells. Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many inflammatory lung diseases such as idiopathic pulmonary fibrosis, acute respiratory distress syndrome, cystic fibrosis and asthma. The imbalance and/or genetic variation in antioxidant γ‐GCS and pro‐inflammatory versus antioxidant genes in response to oxidative stress and inflammation in some individuals may render them more susceptible to lung inflammation. Knowledge of the mechanisms of GSH regulation and balance between the release and expression of pro‐ and anti‐inflammatory mediators could lead to the development of novel therapies based on the pharmacological manipulation of the production as well as gene transfer of this important antioxidant in lung inflammation and injury. This review describes the redox control and involvement of nuclear factor‐κB and activator protein‐1 in the regulation of cellular glutathione and γ‐glutamylcysteine synthetase under conditions of oxidative stress and inflammation, the role of glutathione in oxidant‐mediated susceptibility/tolerance, γ‐glutamylcysteine synthetase genetic susceptibility and the potential therapeutic role of glutathione and its precursors in protecting against lung oxidant stress, inflammation and injury.

show abstract

“…From these results, it might be considered that the cecal or intestinal GSH level would probably be one of the simplest factors to change the GSH level in the liver or plasma. This expectation would be further supported by the suggestion of previous reports that the GSH in the intestine may contribute to an increase of GSH levels in the intestine and in other organs, in particular for the treatment of disease-processes involving oxidative or electrophilic damage (41,42). Still now, the reason why dietary Gelidium sp., TDF, SDF, DFFC or deionized DFFC increased the GSH level of cecal contents is unknown, although there is a report that Gracilaria tikvahiae (red algae) may have a factor which raises the liver GSH level (43).…”

Section: Discussionmentioning

confidence: 58%

Effects of Various Kinds of Edible Seaweeds in Diets on the Development of D-Galactosamine-Induced Hepatopathy in Rats

Kawano

Egashira

Sanada

2007

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

SummaryIn the present study we investigated the effects of 11 kinds of edible seaweeds (6 brown and 5 red algae) which contain characteristic seaweed dietary fibers on the induction of D -GalN ( D -galactosamine)-hepatopathy in rats (Exps. 1 and 2). Then, the efficacy of various components prepared from Gelidium sp., which was found to alleviate the hepatopathy in Exps. 1 and 2, was examined (Exp. 3). The rats were fed the diets containing various kinds of seaweeds (Exps. 1 and 2), or several components of Gelidium sp. such as total dietary fiber (TDF), soluble dietary fiber (SDF), insoluble dietary fiber (IDF) and dietary fiber-free components (DFFC) (Exp. 3), for 8 d. The rats in all experiments were injected with D -GalN (800 mg/kg body weight) intraperitoneally at the 7th day to induce liver injury and were sacrificed 24 h after the injection of D -GalN. The serum transaminase activities (ALT and AST) and lactate dehydrogenase (LDH) were determined to evaluate the levels of hepatopathy. In Exp. 3, the total GSH concentration in the liver, plasma and cecal contents and organic acid concentration in cecal contents were also evaluated. In Exps. 1 and 2, repressive effects against D -GalN-hepatopathy were shown by four seaweeds Laminaria sp., Gelidium sp., Sargassum fulvellum and Eisenia bicyclis . In Exp. 3, it was found that protective activity in Gelidium sp. against D -GalN-hepatopathy existed not only in the SDF but also in the DFFC fraction. The results in Exp. 3 also indicated that the total GSH but not organic acid concentration in the cecal contents were significantly correlated with serum AST activity, suggesting that the protective effect of Gelidium sp. on D -GalN-hepatopathy in rats is related to GSH metabolism in the intestine. Key Words seaweed, D -galactosamine, Gelidium , agar, glutathione This research was conducted for investigation of the influence of seaweeds on the development of D -galactosamine-induced hepatopathy ( D -GalN-hepatopathy) in rats. Because D -GalN-hepatopathy resembles human acute viral hepatitis histologically, D -galactosamine ( DGalN) intoxication is used as an animal model of fulminant hepatic failure ( 1 , 2 ). D -GalN is converted to UDP-D -GalN by the enzymes in the galactose metabolic pathway in the liver ( 3 ). The exhaustion of UTP caused by the UDP-D -GalN formation process is accompanied by a decrease on hepatocellular UDP, UTP, and UDP-glucose levels ( 4 -6 ). Then, D -GalN prevents the synthesis of RNA and protein in the liver, which leads to a defect in some important cell membrane proteins. Besides the above-mentioned causes, the D -GalN-induced-hepatopathy is thought to be also induced by the increase of mesentery permeability of endotoxin which is a kind of natural hepatotoxin in the intestine ( 7 , 8 ). According to previous studies, bacterial translocation in D -GalNhepatopathy was reduced by intestinal excision or use of an antibiotic which reduces intestinal bacteria in the animals before D -GalN-treatment ( 9 , 10 ). In other reports, medication with g...

show abstract

Glutathione transport system in human small intestine epithelial cells

Cited by 65 publications

References 33 publications

Exogenous Glutathione Completes the Defense against Oxidative Stress in Haemophilus influenzae

Exogenous Glutathione Completes the Defense against Oxidative Stress in Haemophilus influenzae

Oxidative stress and regulation of glutathione in lung inflammation

Effects of Various Kinds of Edible Seaweeds in Diets on the Development of D-Galactosamine-Induced Hepatopathy in Rats

Contact Info

Product

Resources

About