Identification of amyloid beta-peptide responsive genes by cDNA microarray technology: involvement of RTP801 in amyloid beta-peptide toxicity.
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.
Kim
Jae-Ryong
JR
Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Korea. kimjr@med.yu.ac.kr
Lee
Seung-Rock
SR
Chung
Hyun Jin
HJ
Kim
Seongyong
S
Baek
Suk-Hwan
SH
Kim
Jung Hye
JH
Kim
Yong-Sun
YS
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000633:toxicity*; D001483:Base Sequence; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D000084622:Sestrins
D016229:Amyloid beta-Peptides; D018076:DNA, Complementary; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C469991:DDIT4 protein, human; C465398:SESN2 protein, human; D000084622:Sestrins; C114997:STC2 protein, human