J Korean Neurol Assoc.  2003 Aug;21(4):401-407.

Involvements of Oxidative Stress in beta-amyloid Peptide: induced Cytotoxicity in PC12 Cells

• Lee JK
• Kim C
• Kim TJ
• Kim BH
• Kim S
• Hah JS
• Kim JH
• Kim JR

Abstract

BACKGROUND
Alzheimer's disease is a neurodegenerative disorder characterized by the extracellular deposition of beta-amyloid peptide(Abeta) in the brain, presumed to play a pathogenic role. However, the precise molecular mechanisms of its neurotoxicity are not fully understood. METHODS: Abeta-mediated cytotoxicity in neuronal cell lines (PC12, SH-SY5Y, IMR32, and U87) was measured by an MTT assay. NF-kappaB activation by Abetawas examined by a luciferase assay and apoptosis induced by Abetawas measured by cytoplasmic DNA fragmentations. RESULTS: Abetacytotoxicity in the tested cell lines was more prominent in the absence of serum than in the presence of serum in culture media. PC12 cells showed the highest sensitivity to Abetacytotoxicity among the cell lines. The Abeta(25-35) cytotoxicity in PC12 cells was increased in a dose-dependent manner. For convincing oxidative stress involved in Abetacytotoxicity, antioxidants such as DTT, GSH, vitamin C, or NAC were pretreated. GSH protected PC12 cells from Abetacytotoxicity, but DTT or NAC did not. Abeta (25-35) treatment to PC12 cells increased the NF-kappaB activity in a dose-dependent manner. Cytoplasmic DNA fragmentations, one of the apoptotic indicators, were increased at lower concentrations of Abeta(25-35) from 0.01 to 0.1 microM, however, dose-dependent increments of DNA fragmentations were not observed at higher concentrations from 1 to 10 microM. CONCLUSIONS: From these results, Abeta-induced cytotoxicity in PC12 cells might be mediated by oxidative stress.

Keyword

Alzheimer disease; Amyloid beta-protein; Oxidative stress; PC12 cells

MeSH Terms

Alzheimer Disease
Amyloid beta-Peptides
Animals
Antioxidants
Apoptosis
Ascorbic Acid
Brain
Cell Line
Culture Media
Cytoplasm
DNA
Luciferases
Neurodegenerative Diseases
Neurons
NF-kappa B
Oxidative Stress*
PC12 Cells*
Amyloid beta-Peptides
Antioxidants
Ascorbic Acid
Culture Media
DNA
Luciferases
NF-kappa B