Fermented papaya preparation attenuates beta-amyloid precursor protein: beta-amyloid-mediated copper neurotoxicity in beta-amyloid precursor protein and beta-amyloid precursor protein Swedish mutation overexpressing SH-SY5Y cells

Neuroscience. 2006 Nov 17;143(1):63-72. doi: 10.1016/j.neuroscience.2006.07.023. Epub 2006 Sep 8.

Abstract

Recent studies indicate that the deposition of beta-amyloid (Abeta) is related in the pathogenesis of Alzheimer's disease (AD), but the underlying mechanism is still not clear. The abnormal interactions of Abeta with metal ions such as copper are implicated in the process of Abeta deposition and oxidative stress in AD brains. In the present study, we established a new AD model, using which we found that copper triggered the Abeta neurotoxicity in SH-SY5Y cells overexpressing the Swedish mutant form of human APP (APPsw) in a concentration dependent manner. Fermented papaya preparation (FPP) has shown high free radical scavenging ability in vivo and in vitro. FPP post-treatment increased cell viability and decreased the intracellular [Ca2+]i, reactive oxygen species (ROS) generation such as hydroxyl free radical and superoxide anion and nitric oxide (NO) accumulation in the cell. Our results also show that FPP prevents the cell apoptosis through bax/bcl-2 sensitive pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Analysis of Variance
  • Apoptosis / drug effects
  • Blotting, Western / methods
  • Calcium / metabolism
  • Carica / chemistry*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Copper / metabolism*
  • Copper / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme-Linked Immunosorbent Assay / methods
  • Gene Expression Regulation / genetics
  • Humans
  • Mutation*
  • Neuroblastoma
  • Nitric Oxide Synthase / metabolism
  • Plant Proteins / pharmacology*
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Transfection / methods

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Plant Proteins
  • RNA, Messenger
  • Reactive Oxygen Species
  • Thiobarbituric Acid Reactive Substances
  • Copper
  • Nitric Oxide Synthase
  • Calcium