Oxidative stress involvement in manganese-induced alpha-synuclein oligomerization in organotypic brain slice cultures

Xu, Bin; Wu, Shengwen; Lu, Chun-Wei; Deng, Yu; Liu, Wei; Wei, Yangang; Yang, Tianyao; Xu, Zhenbo

doi:10.1016/j.tox.2013.01.006

Cited by 50 publications

(43 citation statements)

References 29 publications

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“…Oral treatment with NAC decreases αS levels in the brain and partially protects against loss of DAergic neurons associated with overexpression of αS in αS-overexpressing mice [13]. Moreover, manganese-induced αS oligomerization was also partially alleviated by pretreatment with GSH and aggravated by H 2 O 2 pretreatment [18].…”

Section: Discussionmentioning

confidence: 94%

Effect of Alteration of Glutathione Content on Cell Viability in α-Synuclein-Transfected SH-SY5Y Cells

Tanaka¹,

Sonoda²,

Asanuma³

2017

APD

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It is well known that α-synuclein (αS) plays an important role in the pathogenesis of Parkinson's disease (PD). Moreover, oxidative stress is also thought to be an important factor in PD due to induction of dopaminergic neuronal cell death by free radicals and enhancement of αS fibrillation by oxidized stress. In the present study, to clarify the role of glutathione (GSH), an intracellular antioxidant, on the molecular mechanism of αS-induced cell injury, we examined the effects of L-buthionine-SR-sulfoximine (BSO), a GSH synthase inhibitor, with or without N-acetyl-L-cysteine (NAC), a source of GSH, on αS-induced cell injury in human neuroblastoma SH-SY5Y cells. Treatment with BSO significantly reduced the cell viability of both empty-vector-and αS-transfected SH-SY5Y cells in a dose-dependent manner (p < 0.01), although the ratio of αS-induced reduction of cell viability in α-syn-transfected cells was much greater than that in empty-vector-transfected cells. Moreover, BSO significantly reduced the intracellular total GSH level in both types of transformant cells. However, NAC significantly prevented BSO-induced reduction of both cell viability and GSH level in the αS-transfected cells. These findings suggest that GSH plays an important role in αS-induced cell injury by reducing cell viability.

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Section: Discussionmentioning

confidence: 94%

Effect of Alteration of Glutathione Content on Cell Viability in α-Synuclein-Transfected SH-SY5Y Cells

Tanaka¹,

Sonoda²,

Asanuma³

2017

APD

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“…Multiple lines of proofs have shown that α-syn can be transformed from its normal structure into an unusual disease-associated structure influenced by many factors containing inhesion factors and external factors [6,7,88,93,94]. On the one hand, within α-syn itself, some of its mutations can induce a more toxic effect on DA neurons and were more vulnerable to aggregation [88,95,96].…”

Section: α-Synuclein Aggregation and Parkinson Diseasementioning

confidence: 99%

Catechol Tetrahydroisoquinolines Enhance a-Synuclein Aggregation and Specify the Neurotoxicity to Dopaminergic Neurons

Chen¹,

Lu²,

Duan³

et al. 2017

J Alzheimers Dis Parkinsonism

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“…Mn has been previously shown to induce a-synuclein aggregation. [90][91][92][93][94][95][96][97] Cell lines overexpressing a-synuclein are more vulnerable to Mn toxicity, leading to cell death by apoptosis. 93,94 In addition, it has been reported that Mn up-regulates a-synuclein expression in SH-SY5Y neuroblastoma cells, in brain slices, in C. elegans, 92 in transgenic mice, and in the cortex of nonhuman primates.…”

Section: A-synucleinmentioning

confidence: 99%

“…A compelling evidence of the involvement of oxidative stress in Mn-induced a-synuclein aggregation posits that glutathione (GSH) pre-treatment alleviates its oligomerization whereas H 2 O 2 aggravated it. 97 In a different approach, Xu et al silenced a-synuclein in brain slices and observed that this alleviated Mn-induced ER stress, thus reducing apoptosis in neuronal cells. 96 This provides one putative hypothesis for Mn-induced a-synuclein aggregation because Mn induces damage to ER, impairing the proper unfolded protein response, and thus affecting the degradation of the olygomers.…”

Section: A-synucleinmentioning

confidence: 99%

Manganese and Oxidative Stress

Ávila¹,

Farina²,

Rocha³

et al. 2014

Manganese in Health and Disease

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Although reactive oxygen species (ROS) are known to play crucial roles in maintaining cellular homeostasis, either an excessive increase in their production or a decrease of their detoxification causes oxidative stress, which is characterized as a disturbance in the pro-oxidant/antioxidant balance in favor of the former, leading to cellular damage. This chapter delves into the relationship between manganese (Mn) toxicity and oxidative stress. Although Mn has central physiological roles as cofactor of several enzymes, including antioxidant enzymes (i.e. Mn-superoxide dismutase), this chapter focuses on the pro-oxidative properties of Mn, presenting and discussing literature data concerning its effects on mitochondrial functioning, dopamine oxidation, and antioxidant defenses. The potential use of antioxidant approaches to mitigate Mn-induced toxicity is also presented.

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Oxidative stress involvement in manganese-induced alpha-synuclein oligomerization in organotypic brain slice cultures

Cited by 50 publications

References 29 publications

Effect of Alteration of Glutathione Content on Cell Viability in α-Synuclein-Transfected SH-SY5Y Cells

Effect of Alteration of Glutathione Content on Cell Viability in α-Synuclein-Transfected SH-SY5Y Cells

Catechol Tetrahydroisoquinolines Enhance a-Synuclein Aggregation and Specify the Neurotoxicity to Dopaminergic Neurons

Manganese and Oxidative Stress

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