Molecular and Cellular Biochemistry

, Volume 337, Issue 1–2, pp 39–51 | Cite as

Chitosan prevents oxidative stress-induced amyloid β formation and cytotoxicity in NT2 neurons: involvement of transcription factors Nrf2 and NF-κB

  • Fariba Khodagholi
  • Bahareh Eftekharzadeh
  • Nader Maghsoudi
  • Parisa Fathi Rezaei
Article

Abstract

Increased oxidative stress is a widely accepted factor in the development and progression of Alzheimer’s disease. Here, we introduce chitosan, an antioxidant oligosaccharide, as a protective agent against H2O2/FeSO4-induced cell death in the NT2 neural cell line. Chitosan not only protects the neurons against cell death, as measured by MTT and caspase-3 activity, but also decreases amyloid β formation. NT2 neurons can be used to elucidate the relationship between oxidative stress and Aβ formation. We induced Aβ formation through oxidative stress in NT2 neurons and studied the effect of chitosan. We demonstrate that chitosan can be neuroprotective by suppressing Aβ formation. We further show that chitosan exerts its protective effect by up-regulation of HO-1, γ-GCS, Hsp-70, and Nrf2, while it inhibits activation of caspase-3 and NF-κB. Chitosan or chitosan derivatives have potential value as neuroprotective agents, particularly with regard to oxidative stress.

Keywords

Alzheimer’s disease Amyloid beta Chitosan NF-κB Nrf2 NT2 neurons 

Abbreviations

AD

Alzheimer’s disease

AREs

Antioxidant response elements

DMEM

Dulbecco’s modified Eagle’s medium

DTT

Dithiothreitol

DTNB

Dithionitrobenzoic acid

ECL

Electrochemiluminescence

ELISA

Sandwich enzyme-linked immunosorbent

γ-GCS

γ-glutamylcysteine synthetase

HO-1

Hemeoxigenase-1

Hsp-70

Heat shock protein-70

MTT

3-[4, 5-dimethylthiazol-2-yl]-2, 5-dephenyl tetrazolium bromide

NF-κB

Nuclear factor- κB

Nrf2

Nuclear factor-erythroid 2 p45-related factor 2

PBS

Phosphate buffered saline

PMSF

Phenylmethanesulfonyl fluoride

tBHQ

tert-butylhydroquinone

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Fariba Khodagholi
    • 1
  • Bahareh Eftekharzadeh
    • 1
  • Nader Maghsoudi
    • 1
  • Parisa Fathi Rezaei
    • 1
  1. 1.Neuroscience Research CenterShahid Beheshti University of Medical ScienceTehranIran

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