当前位置： SCI文献检索 > NEUROTOXICITY RESEARCH期刊下所有文献 > Methylglyoxal-Induced Protection Response and Toxicity: Role of Glutathione Reductase and Thioredoxin Systems.

Methylglyoxal-Induced Protection Response and Toxicity: Role of Glutathione Reductase and Thioredoxin Systems.

Abstract：

:Thioredoxin (Trx) and glyoxalase (Glo) systems have been suggested to be molecular targets of methylglyoxal (MGO). This highly reactive endogenous compound has been associated with the development of neurodegenerative pathologies and cell death. In the present study, the glutathione (GSH), Trx, and Glo systems were investigated to understand early events (0.5-3 h) that may determine cell fate. It is shown for the first time that MGO treatment induces an increase in glutathione reductase (GR) protein in hippocampal slices (1 h) and HT22 nerve cells (0.5 and 2.5 h). Thioredoxin interacting protein (Txnip), thioredoxin reductase (TrxR), Glo1, and Glo2 were markedly increased (2- to 4-fold) in hippocampal slices and 1.2- to 1.3-fold in HT22 cells. This increase in protein levels in hippocampal slices was followed by a corresponding increase in GR, TrxR, and Glo1 activities, but not in HT22 cells. In these cells, GR and TrxR activities were decreased by MGO. This result is in agreement with the idea that MGO can affect the Trx/TrxR reducing system, and now we show that GR and Txnip can also be affected by MGO. Impairment in the GR or TrxR reducing capacity can impair peroxide removal by glutathione peroxidase and peroxiredoxin, as both peroxidases depend on reduced GSH and Trx, respectively. In this regard, inhibition of GR and TrxR by 2-AAPA or auranofin, respectively, potentiated MGO toxicity in differentiated SH-SY5Y cells. Overall, MGO not only triggers a clear defense response in hippocampal slices and HT22 cells but also impairs the Trx/TrxR and GSH/GR reducing couples in HT22 cells. The increased MGO toxicity caused by inhibition of GR and TrxR with specific inhibitors, or their inhibition by MGO treatment, supports the notion that both reducing systems are relevant molecular targets of MGO.

journal_name

Neurotox Res

journal_title

Neurotoxicity research

authors

Schmitz AE,de Souza LF,Dos Santos B,Maher P,Lopes FM,Londero GF,Klamt F,Dafre AL

doi

10.1007/s12640-017-9738-5

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

340-350

issue

eissn

1029-8428

issn

1476-3524

pii

10.1007/s12640-017-9738-5

journal_volume

pub_type

杂志文章

在线工具

Methylglyoxal-Induced Protection Response and Toxicity: Role of Glutathione Reductase and Thioredoxin Systems.