Brain glutathione

Kaplan E. and Ansari K. (1984). Reduction of polyunsaturated fatty acid hydroperoxides by human brain glutathione peroxidase. Lipids 19 784-789. 

It is proposed that a brain glutathione deficit leads to the depression of N-methyl-D-aspartate (NMDA) responses and affect synaptic contacts in catecholamine innervated regions. 

Castagne V, Rougemont M, Cuenod M, Do KQ. 2004b. Low brain glutathione and ascorbic add associated with dopamine uptake inhibition during rat s development induce long-term cognitive deficit Relevance to schizophrenia. Neurobiol Dis 15 93-105. 

Heales SJ, Davies SE, Bates TE, Clark JB. 1995. Depletion of brain glutathione is accompanied by impaired mitochondrial function and decreased N-acetyl aspartate concentration. Neurochem Res 20 31-38. 

Klaidman, L.K., Adams, J.D., Jr., Cross, R., Pazdemik, T.L., Samson, F. (2003). Alterations in brain glutathione homeostasis induced by the nerve gas soman. Neurotox. Res. 5 177-82. Klegeris, A., McGeer, E.G., McGeer, P.L. (2007). Therapeutic approaches to inflammation in neurodegenerative disease. Curr. Opin. Neurol. 20 351-7. 

Alvarez de Laviada T, Romero FJ, Anton V, et al. 1987. A simple microassay for the determination of hydrazine in biological samples. Effect of hydrazine and isoniazid on liver and brain glutathione. J Anal Toxicol 11 260-262. 

Vescovi A, Gebbia M, Cappelletti G, et al. 1989. Interactions of manganese with human brain glutathione-... 

Pileblad, E., Miagnusson, T. and Fornstedt, B. (1991) Reduction of brain glutathione by L-buthionine sulfoximine potentiates the dopamine-depleting action of 6-hydroxydopamine in rat striatum. J. Neurochem. 52 978-980. 

Dysfunction of Complex 1 respiratory chain enzyme and ultrastructural damage in the hippocampal mitochondria is seen in kainite-induced SE in rats (Chuang et al., 2(X)4). A key player in mitochondrial oxidative phosphorylation. Complex I is a major source of superoxide and its dysfunction may increase mitochondrial reactive oxygen species (ROS) production and redox signaling (Taylor et al., 2(X)3). The perforant path stimulation model shows mitochondrial dysfunction and decreased brain glutathione (Cock et al., 2002). Pilocarpine-treated rats show selective decline in Complexes 1 and IV activity in hippocampal CAland CA3 subfields (Kudin et al., 2002). This pattern of complex 1 deficiency in CA3 region is also seen in humans (Kunz et al., 2000). 

However, resveratrol was not detectable in the brain, but the precise mechanisms by which it reduces Ap pathology was not elucidated however, it did alter brain glutathione levels. Using a scaling factor of 0.08, the authors find a human equivalent of 1.68 g per day for a 70-kg person. 

Lopez-Torres, M., Perez-Campo, R., Fernandez, A., Barba, C., and Barja de Quiroga, G., 1993a, Brain glutathione reductase induction increases early survival and decreases lipofuscin accumulation in aging frogs. J. Neurosci. Res. 34 233-242. 

Figure 15.11 Possible scheme for the formation of free radicals from the metabolism of dopamine. Normally hydrogen peroxide formed from the deamination of DA is detoxified to H2O along with the production of oxidised glutathione (GSSG) from its reduced form (GSH), by glutathione peroxidase. This reaction is restricted in the brain, however, because of low levels of the peroxidase. By contrast the formation of the reactive OH-radical (toxification) is enhanced in the substantia nigra because of its high levels of active iron and the low concentration of transferin to bind it. This potential toxic process could be enhanced by extra DA formed from levodopa in the therapy of PD (see Olanow 1993 and Olanow et al. 1998)...

Allen JW, Shanker G, Aschner M. 2001. Methyhnercury inhibits the in vitro uptake of the glutathione precursor, cystine, in ashocytes, but not in neurons. Brain Res 894 131-140. 

The free-radical defence mechanisms utilized by the brain are similar to those found in other tissues. The enzymes SOD, catalase, glutathione peroxidase, and the typical radical scavengers, ascorbate, vitamin E and vitamin A are present in the brain, as they are in peripheral tissues. However, the brain may actually be slightly deficient in some of these defence mechanisms when compared to the amounts present in other tissues. 

Marker, H.S., Weiss, C., Silides, D.J., and Cohen, G. (1981). Coupling of dopamine oxidation (monoamine oxidase activity) to glutathione oxidation via the generation of hydrogen peroxide in rat brain homogenates. J. Neurochem. 36, 589-593. 

Hydroxydopamine (6-OHDA) is a neurotoxin that destroys catecholaminergic neurons in the brain. This toxicity is believed to be related to the production of ROS by the neurotoxin. Rats were fed chronically with vitamin E and then challenged with 6-OHDA. The usual depletion of SOD and reduced glutathione (GSH) in most brain regions was attenuated by the vitamin E pretreatment. The authors attributed this success to scavenging by the augmented brain levels of vitamin E (Perumal et al., 1992). 

Maker, H.S. Weiss, C. and Brannan. Amine-mediated toxicity The effects of dopamine, norepinephrine, 5-hydroxytryptamine, 6-hydroxy-dopamine, ascorbate, glutathione and peroxide on the in vitro activities of creatine and adenylate kinases in the brain of the rat. 

Simple etching of the capillary end served to decouple the electrophoretic current from that of amperometric detection, permitting quantitation of attomole levels of catecholamines from brain microdialyzates.24 A postcolumn reactor using bromine generated electrochemically in situ has been used in the detection of peptide thiols, such as glutathione and cysteine, separated by capillary electrophoresis.25... 

The most recent attempt to purify sleep factor(s) from sleep-deprived animals started in the 1970s in Japan. A sleep-promoting substance (conveniently named SPS ) was purified from the brain stem of sleep-deprived rats (Nagasaki et al. 1974). The extract contained at least four somnogenic fractions. Subsequent analysis identified SPS-A as uridine (Iriki et al. 1983) and SPS-B as oxidized glutathione (Komoda et al. 1990). 

Hydrophilic peptides and proteins are frequently large molecules they may enter the brain by carrier-mediated transport, receptor-mediated transcytosis, or by adsorptive-mediated transcytosis. Small peptides, such as di- and tripeptides are transported by the specific transporters, PepTl and PepT2, but neither of them is present at the BBB. Nevertheless, there is saturable brain uptake of the tripeptide glutathione and of several opioid peptides, suggesting that specific transporters, as... 

The presence at the BBB of members of the multidrug resistance-associated protein (MRPs) family, whose members preferentially transport anionic compounds, is still controversial. The seven members of the MRP family belong, like P-gp, to the ATP-binding cassette (ABC) protein superfamily. Mrpl has been found at the BBB in isolated rat brain capillaries, primary cultures of brain capillary endothelial cells and in immortalized capillary endothelial cells, but not in human brain capillaries [59]. Another member, MRP2 has been found at the luminal membrane of the brain endothelial cells [60]. However, further studies are required to show that there are MRP transporters at the BBB (Figure 15.5). As for P-gp, a functional Mrpl was found in primary cultured rat astrocytes [56] and it has been shown to take part in the release of glutathione disulfide from brain astrocytes under oxidative stress [61]. 

Aliosman, F., Caughlan, J., and Gray, G.S. (1989) Diseased DNA intrastrand cross-linking and cytotoxicity induced in human brain tumor cells by 1,3-fcis(2-chlorocthyl)-1 -nitrosourea after in vitro reaction with glutathione. Cancer Res. 49, 5954. 

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