PMID- 21356235 OWN - NLM STAT- MEDLINE DCOM- 20110901 LR - 20131121 IS - 1879-0003 (Electronic) IS - 0141-8130 (Linking) VI - 48 IP - 5 DP - 2011 Jun 1 TI - Chitooligosaccharide-mediated neuroprotection is associated with modulation of Hsps expression and reduction of MAPK phosphorylation. PG - 726-35 LID - 10.1016/j.ijbiomac.2011.02.011 [doi] AB - 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. CI - Copyright (c) 2011 Elsevier B.V. All rights reserved. FAU - Joodi, Golsa AU - Joodi G AD - Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Ansari, Niloufar AU - Ansari N FAU - Khodagholi, Fariba AU - Khodagholi F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110226 PL - Netherlands TA - Int J Biol Macromol JT - International journal of biological macromolecules JID - 7909578 RN - 0 (Antioxidants) RN - 0 (Heat-Shock Proteins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Neuroprotective Agents) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Reactive Oxygen Species) RN - 0 (bcl-2-Associated X Protein) RN - 9012-76-4 (Chitosan) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.4.22.- (Caspase 3) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Apoptosis/drug effects MH - Calcium/metabolism MH - Caspase 3/metabolism MH - Cell Differentiation/drug effects MH - Cell Line, Tumor MH - Chitosan/*analogs & derivatives/*pharmacology MH - Enzyme Activation/drug effects MH - *Gene Expression Regulation/drug effects MH - Heat-Shock Proteins/*metabolism MH - Mitogen-Activated Protein Kinases/*metabolism MH - NF-E2-Related Factor 2/metabolism MH - Neuroprotective Agents/*pharmacology MH - Oxidative Stress/physiology MH - Phosphorylation/drug effects MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Rats MH - Reactive Oxygen Species/metabolism MH - Superoxide Dismutase/metabolism MH - bcl-2-Associated X Protein/metabolism EDAT- 2011/03/02 06:00 MHDA- 2011/09/02 06:00 CRDT- 2011/03/02 06:00 PHST- 2010/12/18 00:00 [received] PHST- 2011/02/14 00:00 [revised] PHST- 2011/02/21 00:00 [accepted] PHST- 2011/03/02 06:00 [entrez] PHST- 2011/03/02 06:00 [pubmed] PHST- 2011/09/02 06:00 [medline] AID - S0141-8130(11)00079-1 [pii] AID - 10.1016/j.ijbiomac.2011.02.011 [doi] PST - ppublish SO - Int J Biol Macromol. 2011 Jun 1;48(5):726-35. doi: 10.1016/j.ijbiomac.2011.02.011. Epub 2011 Feb 26.