title: Chitooligosaccharide-mediated neuroprotection is associated with modulation of Hsps expression and reduction of MAPK phosphorylation.
abstract: There is mounting evidence implicating the role of oxidative stress induced by reactive oxygen species (ROS) in neurodegenerative disease, including Alzheimer's disease. In this study we aimed to investigate the possible protective effect of chitooligosaccharide (COS), an antioxidant oligosaccharide, on hydrogen peroxide induced apoptosis in NGF-differentitated rat pheochromocytoma (PC12) cells. COS treatment reversed the decrease of cell viability induced by H(2)O(2) and this was associated with diminished intracellular ROS and decreased level of cytosolic Ca(2+). Additionally, COS contributed to up-regulation of Bcl-2, down regulation of Bax protein and reduction of cleaved Caspase-3 protein. COS treatment stabilized Nrf2 in nucleus and increased the Hsp70 level within cell while down-regulated Hsp90 expression. Moreover, COS could inhibit the phosphorylation of different mitogen activated protein kinases (MAPKs), whose aberrant phosphorylation has been implicated in AD. Our findings suggest that heat shock response and MAPK cascades are both involved in cell survival, and by concomitantly regulating both pathways, COS can be a promising agent in treating neurodegenerative diseases.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Golsa
authors.initials: G
authors.lastname: Joodi
authors.forename: Niloufar
authors.initials: N
authors.lastname: Ansari
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D006360:Heat-Shock Proteins; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D048271:Chitosan; D013482:Superoxide Dismutase; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D002118:Calcium