{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T01:49:39Z","timestamp":1784080179523,"version":"3.55.0"},"reference-count":47,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T00:00:00Z","timestamp":1517875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2018,2,6]]},"abstract":"<jats:p>Urea cycle enzymes may play important yet poorly characterized roles in Alzheimer\u2019s disease (AD). Our previous results showed that amyloid-\u03b2 (A\u03b2) affects urea cycle enzymes in rat pheochromocytoma (PC12) cells. The aim of the present study was to investigate the changes in arginases, other urea cycle enzymes, and nitric oxide synthases ( NOSs) in PC12 cells transfected with A\u03b2PP bearing the double \u2018Swedish\u2019 mutation ( APPsw, K670M\/N671L) and in postmortem sporadic AD brain hippocampus; the mutation intensifies A\u03b2 production and strongly associates with AD neuropathology. mRNA expression was analyzed using real-time PCR in cell cultures and DNA microarrays in hippocampal CA1 area of human AD brains. Arginase activity was measured spectrophotometrically, and arginine, ornithine, and citrulline levels by high-performance liquid chromatography. Our data demonstrated that the expression and activity of arginases ( Arg1 and Arg2), as well as the expression of argininosuccinate synthase ( Ass) were significantly reduced in APPsw cells compared to control. However, argininosuccinate lyase ( Asl) was upregulated in APPsw cells. Real-time PCR analysis revealed significant elevation of neuronal nitric oxide synthase ( Nnos) mRNA in APPsw cells, without changes in the endothelial Enos, whereas inducible Inos was undetectable. The changes were found to follow closely those observed in the human hippocampal CA1 region of sporadic AD brains. The changes in enzyme expression were accompanied in APPsw cells by significantly elevated citrulline, ornithine, and arginine. Our findings demonstrate that A\u03b2PP\/A\u03b2 alters arginine metabolism and induces a shift of cellular homeostasis that may support the oxidative\/nitrosative stress observed in AD.<\/jats:p>","DOI":"10.3233\/jad-170427","type":"journal-article","created":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T12:59:19Z","timestamp":1517921959000},"page":"279-291","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Altered Expression of Urea Cycle Enzymes in Amyloid-\u03b2 Protein Precursor Overexpressing PC12 Cells and in Sporadic Alzheimer\u2019s Disease Brain"],"prefix":"10.1177","volume":"62","author":[{"given":"Henryk","family":"J\u0119\u015bko","sequence":"first","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter 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