title: The protective effects of chitooligosaccharides against glucose deprivation-induced cell apoptosis in cultured cortical neurons through activation of PI3K/Akt and MEK/ERK1/2 pathways.
abstract: Chitooligosaccharides (COSs), the biodegradation product of chitosan, possess a wide range of biological activities. In this study, we investigated the influences of COSs on primary cultured cortical neurons exposed to glucose deprivation (GD). The cell viability assessment by MTT assay, in couple with cell apoptosis analysis by Hoechst 33342 and TUNEL staining, indicated that GD-induced cell apoptosis in cultured cortical neurons was attenuated by COSs co-treatment in a dose-dependent manner. Light micrography following tetramethylrhodamine methyl ester staining revealed that COSs protected cultured cortical neurons from GD insult through the stabilization of mitochondrial membrane potentials. COSs co-treatment also led to the increase in Bcl-2/Bax protein ratio and the inhibition of caspase-3 activation in cultured cortical neurons exposed to GD insult. We further found that COSs were able to transiently cause the activation of Akt and ERK1/2 proteins, and anti-apoptotic effects of COSs could be blocked by chemical inhibition of PI3K and MEK. Taken together, the results suggest that COSs hold a promise to serve as a potential neuroprotective agent for treating cerebral ischemic stroke and neurodegenerative diseases.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Xu
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shu
authors.initials: S
authors.lastname: Yu
authors.forename: Yumin
authors.initials: Y
authors.lastname: Yang
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency*; D020287:In Situ Nick-End Labeling; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018696:Neuroprotective Agents; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D009844:Oligosaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; C022616:thiazolyl blue; D005947:Glucose