title: Chitooligosaccharides attenuate Cu2+-induced cellular oxidative damage and cell apoptosis involving Nrf2 activation.
abstract: Alzheimer's disease (AD) is one of the common neurodegenerative diseases. Increase of labile copper pool plays an important role in the pathogenesis of AD. Nrf2(NF-E2-related factor-2)-ARE (antioxidant response element) signaling is an important intracellular manner to defend against oxidative stress. In this study, we used SH-SY5Y cells as a model of neuron to test the effect of chitooligosaccharides (COSs) on Cu(2+)-induced oxidative damage. SH-SY5Y cells were treated with different concentrations of COSs (100-800 mg/L) before incubated with Cu(2+). Cell viability and cell damage and apoptosis were assessed. Both extracellular H(2)O(2) and intracellular ROS were measured and the relative levels of Nrf2, phosphorylated Nrf2, and HO-1 were analyzed by Western blotting, and further HO-1 mRNA was relatively quantified by real-time quantitative PCR. The results indicated that Cu(2+)-induced decrease of cell viability and increase of LDH release. In cell-free solution, COSs alone or with Cu(2+) cannot scavenge O(2)(-); however, COSs downregulate the levels of cellular oxidative stress and activated Caspase-3 induced by Cu(2+). Further, the levels of pSer40-Nrf2 protein and both the transcription and the translation of HO-1 gene are dramatically increased in COSs-protective group compared with Cu(2+) damage group. Therefore, these results indicate that Nrf2 activation might be involved in the protection of COSs against Cu(2+)-induced cellular oxidative damage. COSs contribute to the attenuation of oxidative damage and could be used as a nutritional agent for AD treatment.
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, 197#, Beitucheng West Road, Haidian District, Beijing, 100191, China, hanchang@buu.edu.cn.
authors.forename: Han-Chang
authors.initials: HC
authors.lastname: Huang
authors.forename: Liang
authors.initials: L
authors.lastname: Hong
authors.forename: Ping
authors.initials: P
authors.lastname: Chang
authors.forename: Jiao
authors.initials: J
authors.lastname: Zhang
authors.forename: Shu-Yan
authors.initials: SY
authors.lastname: Lu
authors.forename: Bo-Wen
authors.initials: BW
authors.lastname: Zheng
authors.forename: Zhao-Feng
authors.initials: ZF
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002686:Chitin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048271:Chitosan; D003300:Copper / Q000633:toxicity*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009844:Oligosaccharides; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; D009844:Oligosaccharides; D017382:Reactive Oxygen Species; C493484:oligochitosan; D002686:Chitin; D003300:Copper; D048271:Chitosan