Alginate oligosaccharide protects against endoplasmic reticulum- and mitochondrial-mediated apoptotic cell death and oxidative stress

Biomaterials. 2011 Aug;32(23):5438-58. doi: 10.1016/j.biomaterials.2011.04.024. Epub 2011 May 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry*
  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Apoptosis Inducing Factor / metabolism
  • Apoptosis Inducing Factor / pharmacology
  • Calcium / metabolism
  • Caspase 12 / metabolism
  • Caspase 3 / metabolism
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Glucuronic Acid / chemistry
  • Glutathione / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP90 Heat-Shock Proteins / metabolism
  • Hexuronic Acids / chemistry
  • Hydrogen Peroxide / pharmacology
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Models, Biological
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Oligosaccharides / pharmacology*
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • PC12 Cells
  • Peptide Fragments / pharmacology
  • Phosphorylation / drug effects
  • Poly(ADP-ribose) Polymerases / metabolism
  • Polysaccharide-Lyases / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Aifm1 protein, rat
  • Alginates
  • Amyloid beta-Peptides
  • Apoptosis Inducing Factor
  • Bax protein, rat
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Hexuronic Acids
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, rat
  • Oligosaccharides
  • Peptide Fragments
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • amyloid beta-protein (1-42)
  • bcl-2-Associated X Protein
  • Glucuronic Acid
  • Cytochromes c
  • Hydrogen Peroxide
  • Poly(ADP-ribose) Polymerases
  • Extracellular Signal-Regulated MAP Kinases
  • Caspase 12
  • Caspase 3
  • Polysaccharide-Lyases
  • poly(beta-D-mannuronate) lyase
  • Glutathione
  • Calcium