Peroxidation induced changes in synaptosomal transport of dopamine and γ-aminobutyric acid

Rafałowska, Urszula; Liu, Guangjun; Floyd, Robert A.

doi:10.1016/0891-5849(89)90041-5

Cited by 66 publications

(16 citation statements)

References 33 publications

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“…These glutamate transporters seem to be regulated by the surrounding redox environment [41], and defects in glutamate uptake have been reported both in acute and long-term neurodegenerative pathologies associated with oxidative stress [40]. In control Wistar rats a decrease in the uptake of both GABA and glutamate, under oxidative stress conditions (induced by ascorbate/Fe 2+ ), was observed, which agrees with the results obtained by other investigators [17, 40, 41, 46, 47]. In diabetic GK rat brain synaptosomes, and under oxidizing conditions, the uptake of [ 3 H]GABA was decreased, and the uptake of [ 3 H]glutamate was unaffected, suggesting a protective effect against glutamate-induced neurotoxicity.…”

Section: Discussionsupporting

confidence: 83%

Effect of Oxidative Stress on the Uptake of GABA and Glutamate in Synaptosomes Isolated from Diabetic Rat Brain

et al. 2000

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It has been suggested that increased oxidative stress might be involved in the pathophysiology of diabetic complications. In this study, we investigated the effect of diabetes on the susceptibility of synaptosomes to oxidative stress (induced by the oxidizing pair ascorbate/Fe²⁺) and on the uptake of the amino acid neurotransmitters γ-aminobutyric acid (GABA) and glutamate. We found a lower susceptibility of synaptosomes isolated from Goto-Kakizaki (GK) rats, a model of non-insulin-dependent diabetes mellitus, to lipid peroxidation as compared with synaptosomes isolated from Wistar control rats (6.40 ± 1.05 and 12.14 ± 1.46 nmol thiobarbituric acid reactive substance/mg protein, respectively). The lower susceptibility of GK rat synaptosomes to membrane lipid peroxidation correlates with an increase in synaptosomal vitamin E levels (835 ± 58.04 and 624.26 ± 50.26 pmol/mg protein in diabetic and normal rats, respectively). In the absence of ascorbate/Fe²⁺, no significant differences were observed between the levels of lipid peroxidation of synaptosomes isolated from diabetic and normal rats. Studies of neurotransmitter uptake show that the [³H]glutamate uptake was decreased by about 30% in diabetic GK rats as compared with control Wistar rats, whereas the [³H]GABA uptake was not significantly different from controls. Under oxidizing conditions, the glutamate uptake in diabetic rats was unaffected, and a decreased GABA uptake (41.39 ± 4.41 and 60.96 ± 6.4% of control in GK and Wistar rats, respectively) was observed. We conclude that the increased resistance to oxidative stress in GK rat synaptosomes may be due to the increased vitamin E content and that diabetic state and oxidative stress conditions differentially affected the uptake of the neurotransmitters GABA and glutamate.

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Section: Discussionsupporting

confidence: 83%

Effect of Oxidative Stress on the Uptake of GABA and Glutamate in Synaptosomes Isolated from Diabetic Rat Brain

et al. 2000

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“…The brain is a major consumer of oxygen; therefore, it is an important substrate for oxidation by reactive oxygen species. Peroxidation of nerve endings alters neurotransmitter transport and subsequently affects central nervous system functioning (Rafalowska et al 1989).…”

Section: Discussionmentioning

confidence: 99%

Serum concentrations of antioxidant vitamins and carotenoids are low in individuals with a history of attempted suicide

Zhang

2007

Nutritional Neuroscience

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“…Nervous tissue is very susceptible to oxidative stress, due to its high rate of oxygen consumption, relatively low levels of antioxidant defenses, and a high content of polyunsaturated fatty acids and transition metal ions [3,4]. The increased formation and release of reactive oxygen species (ROS), induces structural and functional alterations of cellular membranes [5].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial function is differentially affected upon oxidative stress

Cardoso

Pereira

Oliveira

1999

Free Radical Biology and Medicine

121

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Abstract-The mechanisms that lead to mitochondrial damage under oxidative stress conditions were examined in synaptosomes treated with ascorbate/iron. A loss of membrane integrity, evaluated by electron microscopy and by LDH leakage, was observed in peroxidized synaptosomes and it was prevented by pre-incubation with vitamin E (150 M) and idebenone (50 M). ATP levels decreased, in synaptosomes exposed to ascorbate/iron, as compared to controls. NADH-ubiquinone oxidoreductase (Cx I) and cytochrome c oxidase (Cx IV) activities were unchanged after ascorbate/ iron treatment, whereas succinate-ubiquinone oxidoreductase (Cx II), ubiquinol cytochrome c reductase (Cx III) and ATP-synthase (Cx V) activities were reduced by 55%, 40%, and 55%, respectively. The decrease of complex II and ATP-synthase activities was prevented by reduced glutathione (GSH), whereas the other antioxidants tested (vitamin E and idebenone) were ineffective. However, vitamin E, idebenone and GSH prevented the reduction of complex III activity observed in synaptosomes treated with ascorbate/iron. GSH protective effect suggests that the oxidation of protein SH-groups is involved in the inhibition of complexes II, III and V activity, whereas vitamin E and idebenone protection suggests that membrane lipid peroxidation is also involved in the reduction of complex III activity. These results may indicate that the inhibition of the mitochondrial respiratory chain enzymatic complexes, that are differentially affected by oxidative stress, can be recovered by specific antioxidants.

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Peroxidation induced changes in synaptosomal transport of dopamine and γ-aminobutyric acid

Cited by 66 publications

References 33 publications

Effect of Oxidative Stress on the Uptake of GABA and Glutamate in Synaptosomes Isolated from Diabetic Rat Brain

Effect of Oxidative Stress on the Uptake of GABA and Glutamate in Synaptosomes Isolated from Diabetic Rat Brain

Serum concentrations of antioxidant vitamins and carotenoids are low in individuals with a history of attempted suicide

Mitochondrial function is differentially affected upon oxidative stress

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