Kim Jae-Ryong, Lee Seung-Rock, Chung Hyun Jin, Kim Seongyong, Baek Suk-Hwan, Kim Jung Hye, Kim Yong-Sun
Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
Exp Mol Med. 2003 Oct 31;35(5):403-11. doi: 10.1038/emm.2003.53.
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.
β-淀粉样肽（Aβ）是阿尔茨海默病发病机制中的致病分子，也是老年斑的主要成分，已知其在体外和体内均具有神经毒性。尽管有证据表明氧化应激、钙稳态改变和/或CDK激活剂参与其中，但这种Aβ介导的神经毒性所涉及的机制尚未完全明确。许多研究表明，Aβ可能通过激活转录因子发挥其毒性作用。因此，我们使用3.1K人类DNA微阵列研究了人神经母细胞瘤CHP134细胞中的Aβ反应性基因。在几个被Aβ上调或下调的基因中，通过半定量RT-PCR证实RTP801、Hi95/ sestrin 2和stanniocalcin 2在细胞中是由Aβ介导的过表达。CHP134细胞中正义RTP801基因的瞬时表达增加了对Aβ细胞毒性的敏感性，而反义RTP801基因的表达则保护细胞免受Aβ毒性。这些结果表明，RTP801可能在Aβ毒性和阿尔茨海默病的发病机制中起重要作用。
