Mitochondrial functions in astrocytes: Neuroprotective implications from oxidative damage by rotenone

Cabezas, Ricardo; El-Bachá, Ramon dos Santos; González, Janneth; Barreto, George E.

doi:10.1016/j.neures.2012.07.008

Cited by 83 publications

(70 citation statements)

References 146 publications

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“…This peroxide is formed predominantly by disproportionation of superoxide which can occur enzyme-independently or is catalyzed by superoxide dismutases [22]. Superoxide itself is generated in mitochondria as byproduct of respiratory chain complexes and enzymes [108] and as product of the NADPH oxidase reaction [109]. Hydrogen peroxide is also formed in the reactions of some oxidases, for example monoamine oxidases [110].…”

Section: Gsh and Peroxide Detoxificationmentioning

confidence: 99%

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 and Peroxide Detoxificationmentioning

confidence: 99%

Glutathione-Dependent Detoxification Processes in Astrocytes

et al. 2014

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“…These lesions may involve secondary excitotoxic oxidative stress and ATP failure mechanisms [11] . Although HD may arise through several mechanisms, there is much evidence for the role of oxidative stress in the development of HD [17] . Reactive oxygen species (ROS) are a family of highly reactive molecules produced by stepwise, enzymatic, one-electron reductions of molecular oxygen, yielding superoxide anions and other species [18] .…”

Section: Introductionmentioning

confidence: 99%

Protopanaxtriol protects against 3-nitropropionic acid-induced oxidative stress in a rat model of Huntington's disease

Gao

Chu

et al. 2015

Acta Pharmacol Sin

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Aim: Protopanaxtriol (Ppt) is extracted from Panax ginseng Mayer. In the present study, we investigated whether Ppt could protect against 3-nitropropionic acid (3-NP)-induced oxidative stress in a rat model of Huntington's disease (HD) and explored the mechanisms of action. Methods: Male SD rats were treated with 3-NP (20 mg/kg on d 1, and 15 mg/kg on d 2-5, ip). The rats received Ppt (5, 10, and 20 mg/kg, po) daily prior to 3-NP administration. Nimodipine (12 mg/kg, po) or N-acetyl cysteine (NAC, 100 mg/kg, po) was used as positive control drugs. The body weight and behavior were monitored within 5 d. Then the animals were sacrificed, neuronal damage in striatum was estimated using Nissl staining. Hsp70 expression was detected with immunohistochemistry. Reactive oxygen species (ROS) generation was measured using dihydroethidium (DHE) staining. The levels of components in the Nrf2 pathway were measured with immunohistochemistry and Western blotting. Results: 3-NP resulted in a marked reduction in the body weight and locomotion activity accompanied by progressive striatal dysfunction. In striatum, 3-NP caused ROS generation mainly in neurons rather than in astrocytes and induced Hsp70 expression. Administration of Ppt significantly alleviated 3-NP-induced changes of body weight and behavior, decreased ROS production and restored antioxidant enzymes activities in striatum. Moreover, Ppt directly scavenged free radicals, increased Nrf2 entering nucleus, and the expression of its downstream products heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidase 1 (NQO1) in striatum. Similar effects were obtained with the positive control drugs nimodipine or NAC. Conclusion: Ppt exerts a protective action against 3-NP-induced oxidative stress in the rat model of HD, which is associated with its anti-oxidant activity.

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“…Astrocyte-neuron interactions are known to secure the survival and normal function of neurons (Jessen 2004). Numerous studies have demonstrated that astrocytes play important neuroprotective roles, in neurodegenerative disorders (reviewed by Singh et al 2011;Cabezas et al 2012) and they have the ability to promote neuronal survival by protecting against reactive oxygen species and other stressors (Lopez et al 2007).…”

Section: Endogenous Glial Cells and Their Role In Spinal Cord Injurymentioning

confidence: 99%