Glutathione Cycle Impairment Mediates Aβ-induced Cell Toxicity

Cardoso, Sandra M.; Oliveira, Catarina R.

doi:10.1080/1071576021000041023

Cited by 30 publications

(15 citation statements)

References 36 publications

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“…Astrocytes provide reduced glutathione, the principal cellular antioxidant (Peuchen et al, 1997;Dringen, 2000). Notably, glutathione cycle impairment has been described after 25-35 A␤ peptide treatment (Casley et al, 2002;Cardoso and Oliveira, 2003). This observation could explain why we noticed a decrease of astrocytic protection after A␤ treatment.…”

Section: Discussionmentioning

confidence: 41%

Astrocyte modulation of in vitro β‐amyloid neurotoxicity

Paradisi

Sacchetti

Balduzzi

et al. 2004

Glia

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In Alzheimer's disease brain, beta-amyloid (Abeta) deposition is accompanied by astrocyte activation, whose role in the pathogenesis of the disease is still unclear. To explore the subject, we compared Abeta neurotoxicity in pure hippocampal cultures and neuronal-astrocytic cocultures, where astrocytes conditioned neurons but were not in contact with them or Abeta. In the presence of astrocytes, neurons were protected from Abeta neurotoxicity. Neuritic dystrophy was reduced, synapses were partially preserved, and apoptosis was contrasted. The protection disappeared when astrocytes were also treated with Abeta, suggesting that Abeta-astrocyte interaction is deleterious for neurons. This was supported by comparing Abeta neurotoxicity in pure neurons and neurons grown on astrocytes. In this case, where astrocytes were also in contact with Abeta, neuritic damage was enhanced and expression of synaptic vesicle proteins decreased. Our results suggest that astrocytes can protect neurons from Abeta neurotoxicity, but when they interact with Abeta, the protection is undermined and neurotoxicity enhanced.

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Section: Discussionmentioning

confidence: 41%

Astrocyte modulation of in vitro β‐amyloid neurotoxicity

Paradisi

Sacchetti

Balduzzi

et al. 2004

Glia

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“…Others reported that the effect of Zn 2+ on preventing caspase-3 activation and apoptotic cell death could be due to the regulation of cellular redox potential involving GSH (Nakatani et al, 2000). This action of Zn 2+ on the glutathione cycle could be relevant, since Aβ 25-35 induces the decrease of the cellular GSH (Cardoso et al, 2003).…”

Section: +mentioning

confidence: 95%

Protective effect of zinc on amyloid-ß 25–35 and 1–40 mediated toxicity

et al. 2005

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Amyloid beta-peptide (Abeta) is widely held to be associated with Alzheimer's disease, the insoluble aggregates of the peptide being the major constituents of senile plaques. In this study, we evaluated the effect of Zn(2+) (5, 50 and 200 microM) on Abeta induced toxicity using the human teratocarcinome (NT2) cell line. Our results proved that 50 and 200 microM Zn(2+) protected NT2 cells from Abeta 25-35 toxicity. Zinc was also shown to be effective by preventing the loss of mitochondrial membrane potential (DeltaPsi(m)) induced by Abeta 25-35, not allowing cytochrome c release from mitochondria, and subsequently, caspase 3 activation. However, when the cells were treated with Abeta 1-40, only Zn(2+) 5 microM had a protective effect. We have further observed that 5 microM Zn(2+) prevented Abeta 1-40 aggregation into a beta-sheet structure. Considering the results presented, we argue that Zn(2+) has a concentration-dependent protective effect.

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“…As previously discussed, the reduction in GSH levels is in accordance with earlier reports from studies with AD brain 28 and also with other in vitro studies. 29 The decrease in GSH levels could further suggest that glutathione participates in the recuperation of reduced GRX1 seen at 24 h (see Figure 1). On the other hand, the recuperation of reduced TRX1, seen at 24 h, could indicate an additional upregulation of the reducing Several reports have shown that Ab induces apoptosis in a number of different models (for a review, see Small et al…”

Section: Discussionmentioning

confidence: 99%

“…Ab (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and Ab were purchased from Sigma-Aldrich (Stockholm, Sweden). Ab(1-42) was from US Peptide (Rancho Cucamonga, CA, USA) and dissolved in serum-free minimum essential medium (MEM).…”

Section: Methodsmentioning

confidence: 99%

Involvement of glutaredoxin-1 and thioredoxin-1 in β-amyloid toxicity and Alzheimer's disease

et al. 2005

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Strong evidence indicates oxidative stress in the pathogenesis of Alzheimer's disease (AD). Amyloid b (Ab) has been implicated in both oxidative stress mechanisms and in neuronal apoptosis. Glutaredoxin-1 (GRX1) and thioredoxin-1 (TRX1) are antioxidants that can inhibit apoptosis signalregulating kinase (ASK1). We examined levels of GRX1 and TRX1 in AD brain as well as their effects on Ab neurotoxicity. We show an increase in GRX1 and a decrease in neuronal TRX1 in AD brains. Using SH-SY5Y cells, we demonstrate that Ab causes an oxidation of both GRX1 and TRX1, and nuclear export of Daxx, a protein downstream of ASK1. Ab toxicity was inhibited by insulin-like growth factor-I (IGF-I) and by overexpressing GRX1 or TRX1. Thus, Ab neurotoxicity might be mediated by oxidation of GRX1 or TRX1 and subsequent activation of the ASK1 cascade. Deregulation of GRX1 and TRX1 antioxidant systems could be important events in AD pathogenesis.

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Glutathione Cycle Impairment Mediates Aβ-induced Cell Toxicity

Cited by 30 publications

References 36 publications

Astrocyte modulation of in vitro β‐amyloid neurotoxicity

Astrocyte modulation of in vitro β‐amyloid neurotoxicity

Protective effect of zinc on amyloid-ß 25–35 and 1–40 mediated toxicity

Involvement of glutaredoxin-1 and thioredoxin-1 in β-amyloid toxicity and Alzheimer's disease

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