Chitosan prevents oxidative stress-induced amyloid beta formation and cytotoxicity in NT2 neurons: involvement of transcription factors Nrf2 and NF-kappaB.
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 H(2)O(2)/FeSO(4)-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 beta formation. NT2 neurons can be used to elucidate the relationship between oxidative stress and Abeta formation. We induced Abeta formation through oxidative stress in NT2 neurons and studied the effect of chitosan. We demonstrate that chitosan can be neuroprotective by suppressing Abeta formation. We further show that chitosan exerts its protective effect by up-regulation of HO-1, gamma-GCS, Hsp-70, and Nrf2, while it inhibits activation of caspase-3 and NF-kappaB. Chitosan or chitosan derivatives have potential value as neuroprotective agents, particularly with regard to oxidative stress.
Khodagholi
Fariba
F
Neuroscience Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran. khodagholi@sbmu.ac.ir
Eftekharzadeh
Bahareh
B
Maghsoudi
Nader
N
Rezaei
Parisa Fathi
PF
D016229:Amyloid beta-Peptides / Q000009:adverse effects* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects*; D003603:Cytotoxins / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D055503:Protein Multimerization / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology
D016229:Amyloid beta-Peptides; D003603:Cytotoxins; D018840:HSP70 Heat-Shock Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; D014157:Transcription Factors; D048271:Chitosan; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D053148:Caspase 3