Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 48, Issue 5, Pages 726-735Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2011.02.011
Keywords
Chitooligosaccharides; Hsp; MAPK; Oxidative stress; PC12 cells
Funding
- Shahid Beheshti University of Medical Sciences
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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 H2O2 and this was associated with diminished intracellular ROS and decreased level of cytosolic Ca2+. 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 wHsp90 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. (C) 2011 Elsevier B.V. All rights reserved.
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