Altered APP Carboxyl-Terminal Processing Under Ferrous Iron Treatment in PC12 Cells

• 영문명: Altered APP Carboxyl-Terminal Processing Under Ferrous Iron Treatment in PC12 Cells
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Chi Hyun Kim Yeong-Min Yoo
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제17권 제3호, 189~195쪽, 전체 7쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2013.01.01

영문 초록

Amyloid-Ղ peptide (AՂ), generated by proteolytic cleavage of the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of Alzheimer s disease (AD). The key step in the generation of AՂ is cleavage of APP by beta-site APP-cleaving enzyme 1 (BACE1). Levels of BACE1 are increased in vulnerable regions of the AD brain, but the underlying mechanism is unknown. In the present study, we reported the effects of ferrous ions at subtoxic concentrations on the mRNA levels of BACE1 and a-disintegrin-and-metalloproteinase 10 (ADAM10) in PC12 cells and the cell responses to ferrous ions. The cell survival in PC12 cells significantly decreased with 0 to 0.3 mM FeCl₂, with 0.6 mM FeCl₂ treatment resulting in significant reductions by about 75%. 4,6-diamidino-2-phenylindole (DAPI) staining showed that the nuclei appeared fragmented in 0.2 and 0.3 mM FeCl₂. APP-Ձ-carboxyl terminal fragment (APP-Ձ-CTF) associations with ADAM10 and APP-Ղ-CTF with BACE1 were increased. Levels of ADAM10 and BACE1 mRNA increased in response to the concentrations of 0.25 mM, respectively. In addition, p-ERK and p-Bad (S112, S155) expressions were increased, suggesting that APP-CTF formation is related to ADAM10/BACE1 expression. Levels of Bcl-2 protein were increased, but significant changes were not observed in the expression of Bax. These data suggest that ion-induced enhanced expression of AMDA10/BACE1 could be one of the causes for APP-Ձ/Ղ-CTF activation.

키워드

ADAM10 APP-Ձ /Ղ -CTF APP processing BACE1 Ferrous iron p-ERK