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2009 | 69 | 3 |
Tytuł artykułu

Mitochondrial and nuclear targets of amyloid wita-evoked oxidative stress

Warianty tytułu
Języki publikacji
PL
Abstrakty
EN
Amyloid β (Aβ) is responsible for mitochondrial failure and biochemical alterations linked to Alzheimer`s disease (AD). To better understand mechanisms of Aβ toxicity we investigated its mitochondrial and nuclear targets, apoptosis-inducing factor (AIF) and Poly(ADP-ribose) polymerase-1 (PARP-1) in PC12 cells transfected with wild type (APPwt) or double Swedish-mutated human Amyloid Precursor Protein gene (APPsw) characterized by different Aβ concentrations. We found close relationship between Aβ level and cyclooxygenase (COX)- and lipoxygenase (LOX)-related free radical formation leading to p65/NF-κB nuclear translocation. COX and LOX inhibitors protected APPsw cells against p65 translocation. Aβ-evoked oxidative stress enhanced mitochondrial AIF level and inhibited PARP-1 in APPsw cells. Nitrosative stress evoked by 0.5 mM sodium nitroprusside (SNP) had no further effect on Aβ-altered PARP-1 activity and mitochondrial AIF level in APPsw cells. However, SNP evoked death of 70–80% of all cell types after 24 h. COX and LOX inhibitors had ameliorating effect in these conditions. Our data indicated that double Swedish mutation in APP signifi cantly increased cell vulnerability to oxidative stress. Enhanced mitochondrial AIF level and PARP-1 inhibition might be responsible for cell survival under oxidative stress evoked by accumulating Aβ in APPsw cells. COX and LOX inhibitors protected the cells against death caused by simultaneous Aβ toxicity and nitrosative stress.
Słowa kluczowe
Wydawca
-
Rocznik
Tom
69
Numer
3
Opis fizyczny
p.341
Twórcy
autor
  • Department of Cellular Signaling, Medical Research Centre Polish Academy of Sciences, Warsaw, Poland
  • Department of Cellular Signaling, Medical Research Centre Polish Academy of Sciences, Warsaw, Poland
autor
  • Department of Neurosurgery, Medical Research Centre Polish Academy of Sciences, Warsaw, Poland
autor
  • Department of Cellulae Signaling, Medical Research Centre Polish Academy of Sciences, Warsaw, Poland
  • Department of Neurosurgery, Medical Research Centre Polish Academy of Sciences, Warsaw, Poland
Bibliografia
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
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