Exp Mol Med.  2003 Oct;35(5):403-411.

Identification of amyloid beta-peptide responsive genes by cDNA microarray technology: Involvement of RTP801 in amyloid beta-peptide toxicity

• Kim JR
• Lee SR
• Chung HJ
• Kim S
• Baek SH
• Kim JH
• Kim YS

Abstract

Amyloid beta-peptide (Abeta), a causative molecule in the pathogenesis of Alzheimer's disease and the main component of senile plaques, is known to be neurotoxic in vitro and in vivo. The mechanisms involved in this Ab-mediated neurotoxicity are not fully understood, although there is evidence to suggest the involvement of oxidative stress, alterations in calcium homeostasis, and/or of CDK activators. Many studies have suggested that Ab may exert its toxic effect via the activation of transcription factors. Therefore, we investigated Ab- responsive genes in human neuroblastoma CHP134 cells using 3.1K human DNA microarrays. Among the several genes overexpressed or repressed by Ab, RTP801, Hi95/sestrin 2, and stanniocalcin 2 were confirmed to be Ab-mediated overexpression in the cells by semiquantitative RT-PCR. Transient expression of the sense RTP801 gene in CHP134 cells increased sensitivity to Abeta cytotoxicity and the expression of the antisense RTP801 gene protected the cells from the Abeta toxicity. These results suggest that RTP801 might play important roles in Abeta toxicity and the pathogenesis of Alzheimer's disease.

MeSH Terms

Alzheimer Disease/genetics/pathology
Amyloid beta-Protein/analysis/*toxicity
Base Sequence
Cell Line, Tumor
DNA, Complementary/analysis/genetics
*Gene Expression Profiling
Gene Expression Regulation/*drug effects
Glycoproteins/genetics
Human
Molecular Sequence Data
Nuclear Proteins/genetics
*Oligonucleotide Array Sequence Analysis
RNA, Messenger/genetics/metabolism
Reverse Transcriptase Polymerase Chain Reaction
Support, Non-U.S. Gov't
Transcription Factors/*genetics/*metabolism