Detoxification of hydrogen peroxide by astrocytes

Dringen, Ralf; Liddell, J.; Knorpp, Thomas; Robinson, Stephen R.

doi:10.1007/1-4020-4456-9_4

Cited by 2 publications

(5 citation statements)

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“…In addition, if the antioxidant defences of astrocytes are compromised, astrocytes are damaged by exogenous and endogenous peroxides in an iron-dependent process [13,14]. Normally however, astrocytes can efficiently detoxify peroxides [1,13,14] and are able to accumulate and store large amounts of iron. The present article provides an overview of the pathways of iron uptake, storage and export by astrocytes and discusses the involvement of these cells in the trafficking of iron in the brain.…”

Section: Introductionmentioning

confidence: 97%

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The Pivotal Role of Astrocytes in the Metabolism of Iron in the Brain

et al. 2007

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Iron is essential for the normal functioning of cells but since it is also capable of generating toxic reactive oxygen species, the metabolism of iron is tightly regulated. The present article advances the view that astrocytes are largely responsible for distributing iron in the brain. Capillary endothelial cells are separated from the neuropil by the endfeet of astrocytes, so astrocytes are ideally positioned to regulate the transport of iron to other brain cells and to protect them if iron breaches the blood-brain barrier. Astrocytes do not appear to have a high metabolic requirement for iron yet they possess transporters for transferrin, haemin and non-transferrin-bound iron. They store iron efficiently in ferritin and can export iron by a mechanism that involves ferroportin and ceruloplasmin. Since astrocytes are a common site of abnormal iron accumulation in ageing and neurodegenerative disorders, they may represent a new therapeutic target for the treatment of iron-mediated oxidative stress.

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Section: Introductionmentioning

confidence: 97%

“…Cells limit this potential by storing excess iron in a redox-inactive form in ferritin, and by quickly converting H 2 O 2 to water through the action of the enzymes catalase and glutathione peroxidase ( Fig. 1; for review see reference [1]). …”

Section: Introductionmentioning

confidence: 99%

The Pivotal Role of Astrocytes in the Metabolism of Iron in the Brain

et al. 2007

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“…Cultured astrocytes have a robust capacity to clear extracellular H 2 O 2 (Dringen et al, 2005, 2006). To investigate the consequences of persistent oxidative stress on the metabolism of astrocytes, we have exposed primary rat astrocyte cultures to a sublethal, sustained concentration of H 2 O 2 .…”

Section: Discussionmentioning

confidence: 99%

“…Although H 2 O 2 is not particularly toxic, it can generate highly reactive hydroxyl radicals in the presence of transition metals such as iron (Halliwell and Gutteridge, 2007). To prevent such reactions, astrocytes have efficient mechanisms for disposing of peroxides, including glutathione peroxidase (GPx) and catalase (Dringen et al, 2005, 2006; Liddell et al, 2006). In addition, they can store iron in a redox‐inactive form in ferritin (Dringen et al, 2007a).…”

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confidence: 99%

“…Cultured astrocytes are highly efficient at removing exogenous hydrogen peroxide, with half‐times in the minute range after a bolus application of the peroxide (Liddell et al, 2006; Dringen et al, 2006). Thus, bolus application of hydrogen peroxide is not a suitable way to investigate the consequences of sustained oxidative stress on the metabolism of glucose via glycolysis in astrocytes.…”

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Sustained hydrogen peroxide stress decreases lactate production by cultured astrocytes

Liddell

Zwingmann

Schmidt

et al. 2009

J of Neuroscience Research

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Oxidative stress and disrupted energy metabolism are common to many pathological conditions of the brain. Because astrocytes play an important role in the glucose metabolism of the brain, we have investigated whether sustained oxidative stress affects astroglial glucose metabolism with cultured primary rat astrocytes as a model system. Cultured astrocytes were exposed to a sustained concentration of approximately 50 muM H(2)O(2) in the presence of [U-(13)C]glucose, and cellular and extracellular contents of lactate and glucose were analysed by enzymatic assays and NMR spectroscopy. Exposure of the cells to sustained H(2)O(2) stress for up to 120 min significantly lowered the rate of lactate accumulation in the media to 61% +/- 14% of that in cultures incubated without peroxide. In addition, the ratio of lactate release to glucose consumption was lowered in peroxide-treated astrocytes to 77% +/- 13% of that in control cells, and the specific activity of glyceraldehyde-3-phosphate dehydrogenase had declined to about 10% of control cells within 90 min. In addition, the (13)C enrichment of intracellular and extracellular [(13)C]lactate was about 30% and 95%, respectively, and was not affected by the presence of peroxide, demonstrating that two metabolic pools of lactate are present in cultured astrocytes. The decreased rate of lactate production by astrocytes that have been exposed to peroxide stress is a new example of an alteration by oxidative stress of an important metabolic pathway in astrocytes. Such alterations could contribute to the pathological conditions that have been connected with oxidative stress and disrupted energy metabolism in the brain.

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Detoxification of hydrogen peroxide by astrocytes

Cited by 2 publications

References 54 publications

The Pivotal Role of Astrocytes in the Metabolism of Iron in the Brain

The Pivotal Role of Astrocytes in the Metabolism of Iron in the Brain

Sustained hydrogen peroxide stress decreases lactate production by cultured astrocytes

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