title: Alginate oligosaccharide protects against endoplasmic reticulum- and mitochondrial-mediated apoptotic cell death and oxidative stress.
abstract: Oxidative stress is a major component of harmful cascades activated in neurodegenerative disorders. We sought to elucidate possible effects of alginate oligosaccharide (AOS) on H(2)O(2)-induced cell death and to determine the underlying molecular mechanisms in neuron-like PC12 cells. We found that AOS treatment protected PC12 cells against H(2)O(2)-induced endoplasmic reticulum (ER) and mitochondrial-dependent apoptotic cell death. AOS promoted Bcl-2 expression, while blocked Bax expression and inhibited H(2)O(2)-induced caspase-3 activation. It also blocked PARP cleavage. AOS acted on key molecules in apoptotic cell death pathway and reduced p53, p38, c-June NH2-terminal kinase phosphorylations, inhibited NFkB, and enhanced Nrf2 activation. These results suggest that treatment of PC12 cells with AOS can block H(2)O(2)-induced oxidative stress and caspase-dependent apoptotic cascades originating from both ER and mitochondria. Our in vivo experiments further confirm the neuroprotective potential of AOS against Aβ-induced neural damage. According to our data, the involvement of caspase-independent pathway in AOS-induced protection appears to be unlikely.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Solaleh Khoramian
authors.initials: SK
authors.lastname: Tusi
authors.forename: Leila
authors.initials: L
authors.lastname: Khalaj
authors.forename: Ghorbangol
authors.initials: G
authors.lastname: Ashabi
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Kiaei
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
mesh_terms: D000464:Alginates / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051033:Apoptosis Inducing Factor / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D053454:Caspase 12 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009844:Oligosaccharides / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011133:Polysaccharide-Lyases / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494831:Aifm1 protein, rat; D000464:Alginates; D016229:Amyloid beta-Peptides; D051033:Apoptosis Inducing Factor; C494828:Bax protein, rat; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006603:Hexuronic Acids; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; D009844:Oligosaccharides; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C075222:amyloid beta-protein (1-42); D051028:bcl-2-Associated X Protein; D020723:Glucuronic Acid; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D053454:Caspase 12; D053148:Caspase 3; D011133:Polysaccharide-Lyases; C016158:poly(beta-D-mannuronate) lyase; D005978:Glutathione; D002118:Calcium