人野生型β-淀粉样蛋白前体蛋白（βAPP）转染的细胞中精氨酸代谢的改变

Title:Altered Arginine Metabolism in Cells Transfected with Human Wild-Type Beta Amyloid Precursor Protein (βAPP)

Volume: 13 Issue: 9

Author(s): Henryk Jęśko, Anna Wilkaniec, Magdalena Cieślik, Wojciech Hilgier, Magdalena Gąssowska, Walter J. Lukiw, Agata Adamczyk

Affiliation:

关键词: Β-淀粉样蛋白，β淀粉样前体蛋白、精氨酸酶，一氧化氮合酶，鸟氨酸循环、尿素循环

摘要: Alterations of enzymes linked to arginine metabolism have been recently implicated in Alzheimer's disease (AD). Despite strong association of arginine changes with nitric oxide (NO) pathway, the impact of amyloid β (Aβ) peptides on arginine degradation and re-synthesis is unknown. In the present study we compared expression levels of arginases (ARG1, ARG2), neuronal, endothelial and inducible NO synthase isoforms (NNOS, ENOS, INOS), enzymes that metabolize arginine or resynthesize it from citrulline and the levels of corresponding amino acids in rat pheochromocytoma (PC12) cells overexpressing human Aβ precursor protein (APPwt cells). Moreover, we investigated the changes in miRNAs responsible for modulation of arginine metabolism in AD brains. Real-time PCR analysis revealed in APPwt cells significant decreases of ARG1 and ARG2 which are responsible for lysing arginine into ornithine and urea; this reduction was followed by significantly lower enzyme activity. NNOS and ENOS mRNAs were elevated in APPwt cells while iNOS was undetectable in both cell lines. The expression of argininosuccinate synthase (ASS) that metabolizes citrulline was down-regulated without changes in argininosuccinate lyase (ASL). Ornithine decarboxylase (ODC), which decarboxylates ornithine to form putrescine was also reduced. Arginine, the substrate for both arginases and NOS, was unchanged in APPwt cells. However, citrulline concentration was significantly higher. Elevated miRNA-9 and miRNA-128a found in AD brain tissues might modulate the expression of ASS and NOS, respectively. Our results indicate that Aβ affects arginine metabolism and this influence might have important role in the pathomechanism of AD.

Cite this article as:

Henryk Jęśko, Anna Wilkaniec, Magdalena Cieślik, Wojciech Hilgier, Magdalena Gąssowska, Walter J. Lukiw, Agata Adamczyk , Altered Arginine Metabolism in Cells Transfected with Human Wild-Type Beta Amyloid Precursor Protein (βAPP), Current Alzheimer Research 2016; 13 (9) . https://dx.doi.org/10.2174/1567205013666160314150348