Elevation of glutathione levels by ammonium ions in primary cultures of rat astrocytes

Murthy, Ch.R.K.; Bender, Alex S.; Dombro, Roy S.; Bai, Ge; Norenberg, Michael D.

doi:10.1016/s0197-0186(00)00028-0

Cited by 50 publications

(31 citation statements)

References 46 publications

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“…Consequently, treatments which increase the GSH concentration in astrocytes should lead to an increase in the rate of cellular GSH export. This has been confirmed for astrocytes that contained higher GSH contents due to a pre-incubation with ammonium [90], arsenate [89], arsenite [91], cadmium chloride [89,91], copper chloride [89,92], copper oxide nanoparticles [93], nitric oxide [94] or with fibroblast growth factor 1 and tertiary butyl hydroquinone [95].…”

Section: Gsh Redox Cyclingmentioning

confidence: 68%

“…3d). This enzyme is expressed and active in Acrylonitrile [157] Ammonium [90,158] Anethole dithiolethione [159] Arsenite [91] Arsenate [89] Cadmium chloride [89,91] Catalpol [160] Copper chloride [89,92] Copper oxide nanoparticles [93] Curcumin Thyroid hormone [169] This [78][79][80]. In addition to Mrp1, astrocytes express a number of other Mrps and other potential GSH exporters in culture and in vivo [43, [81][82][83][84][85][86], but the contribution of these transporters in astrocytic export processes remains to be elucidated.…”

Section: Gsh Redox Cyclingmentioning

confidence: 99%

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Glutathione-Dependent Detoxification Processes in Astrocytes

et al. 2014

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Astrocytes have a pivotal role in brain as partners of neurons in homeostatic and metabolic processes. Astrocytes also protect other types of brain cells against the toxicity of reactive oxygen species and are considered as first line of defence against the toxic potential of xenobiotics. A key component in many of the astrocytic detoxification processes is the tripeptide glutathione (GSH) which serves as electron donor in the GSH peroxidase-catalyzed reduction of peroxides. In addition, GSH is substrate in the detoxification of xenobiotics and endogenous compounds by GSH-S-transferases which generate GSH conjugates that are efficiently exported from the cells by multidrug resistance proteins. Moreover, GSH reacts with the reactive endogenous carbonyls methylglyoxal and formaldehyde to intermediates which are substrates of detoxifying enzymes. In this article we will review the current knowledge on the GSH metabolism of astrocytes with a special emphasis on GSH-dependent detoxification processes.

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Section: Gsh Redox Cyclingmentioning

confidence: 68%

Section: Gsh Redox Cyclingmentioning

confidence: 99%

Glutathione-Dependent Detoxification Processes in Astrocytes

et al. 2014

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“…Likewise, in ammonia polluted water an increase in [GSH] and GSH/GSSH ratio was reported in brain of mudskippers, marked by a decline in GR activity [30]. Gamma-glutamyl cysteine synthetase has also been documented for producing GSH in cells, and an increase in the activity of this enzyme was reported under acute hyperammonemic conditions [88]. Presumably, these additional routes could have contributed to the increase in GSH levels in goldfish and mudskipper exposed to ammonia.…”

Section: Discussionmentioning

confidence: 99%

Anti-Oxidative Defences Are Modulated Differentially in Three Freshwater Teleosts in Response to Ammonia-Induced Oxidative Stress

et al. 2014

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Oxidative stress and the antioxidant response induced by high environmental ammonia (HEA) were investigated in the liver and gills of three freshwater teleosts differing in their sensitivities to ammonia. The highly ammonia-sensitive salmonid Oncorhynchus mykiss (rainbow trout), the less ammonia sensitive cyprinid Cyprinus carpio (common carp) and the highly ammonia-resistant cyprinid Carassius auratus (goldfish) were exposed to 1 mM ammonia (as NH4HCO3) for 0 h (control), 3 h, 12 h, 24 h, 48 h, 84 h and 180 h. Results show that HEA exposure increased ammonia accumulation significantly in the liver of all the three fish species from 24 h–48 h onwards which was associated with an increment in oxidative stress, evidenced by elevation of xanthine oxidase activity and levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA). Unlike in trout, H2O2 and MDA accumulation in carp and goldfish liver was restored to control levels (84 h–180 h); which was accompanied by a concomitant increase in superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase activity and reduced ascorbate content. Many of these defence parameters remained unaffected in trout liver, while components of the glutathione redox cycle (reduced glutathione, glutathione peroxidase and glutathione reductase) enhanced to a greater extent. The present findings suggest that trout rely mainly on glutathione dependent defensive mechanism while carp utilize SOD, CAT and ascorbate as anti-oxidative sentinels. Hepatic cells of goldfish appear to utilize each of these protective systems, and showed more effective anti-oxidative compensatory responses towards HEA than carp, while trout were least effective. The present work also indicates that HEA exposure resulted in a relatively mild oxidative stress in the gills of all three species. This probably explains the almost complete lack of anti-oxidative responses in branchial tissue. This research suggests that oxidative stress, as well as the antioxidant potential clearly differ between salmonid and cyprinid species.

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“…When neuron's GSH gets depleted due to acute ammonia intoxication, the precursors for GSH synthesis are supplied from astrocytes which are supposed to be less susceptible to ROS insult [41]. Furthermore, gamma glutamyl-cystein synthetase is also responsible to produce GSH in the cells, and this enzyme has been reported to be increased in the astrocytes under acute HA condition [43]. Thus, it is likely that these additional routes could contribute for maintaining GSH level in the cortex of chronic HA rats even when GR activity declined significantly (P < 0.01).…”

Section: Discussionmentioning

confidence: 99%

Acute and Chronic Hyperammonemia Modulate Antioxidant Enzymes Differently in Cerebral Cortex and Cerebellum

2007

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Studies on acute hyperammonemic models suggest a role of oxidative stress in neuropathology of ammonia toxicity. Mostly, a low grade chronic type hyperammonemia (HA) prevails in patients with liver diseases and causes derangements mainly in cerebellum associated functions. To understand whether cerebellum responds differently than other brain regions to chronic type HA with respect to oxidative stress, this article compares active levels of all the antioxidant enzymes vis a vis extent of oxidative damage in cerebral cortex and cerebellum of rats with acute and chronic HA induced by intra-peritoneal injection of ammonium acetate (successive doses of 10 x 10(3) & 8 x 10(3) micromol/kg b.w. at 30 min interval for acute and 8 x 10(3) micromol/kg b.w. daily up to 3 days for chronic HA). As compared to the respective control sets, cerebral cortex of acute HA rats showed significant decline (P < 0.01-0.001) in the levels of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) but with no change in glutathione reductase (GR). In cerebellum of acute HA rats, SOD, catalase and GR though declined significantly, GPx level was found to be stable. Contrary to this, during chronic HA, levels of SOD, catalase and GPx increased significantly in cerebral cortex, however, with a significant decline in the levels of SOD and GPx in cerebellum. The results suggest that most of the antioxidant enzymes decline during acute HA in both the brain regions. However, chronic HA induces adaptive changes, with respect to the critical antioxidant enzymes, in cerebral cortex and renders cerebellum susceptible to the oxidative stress. This is supported by approximately 2- and 3-times increases in the level of lipid peroxidation in cerebellum during chronic and acute HA respectively, however, with no change in the cortex due to chronic HA.

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Elevation of glutathione levels by ammonium ions in primary cultures of rat astrocytes

Cited by 50 publications

References 46 publications

Glutathione-Dependent Detoxification Processes in Astrocytes

Glutathione-Dependent Detoxification Processes in Astrocytes

Anti-Oxidative Defences Are Modulated Differentially in Three Freshwater Teleosts in Response to Ammonia-Induced Oxidative Stress

Acute and Chronic Hyperammonemia Modulate Antioxidant Enzymes Differently in Cerebral Cortex and Cerebellum

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