{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:12:47Z","timestamp":1791105167245,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,11,2]],"date-time":"2009-11-02T00:00:00Z","timestamp":1257120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oxidative stress is associated with \u03b2\u2010amyloid peptide (A\u03b2) accumulation in the brains of Alzheimer's disease patients. A\u03b2 is generated upon the sequential proteolytic cleavage of transmembrane amyloid precursor protein (APP) by two membrane\u2010bound proteases, \u03b2\u2010secretase (BACE1) and the \u03b3\u2010secretase complex comprising presenilin 1 (PS1), nicastrin, APH\u20101 and PEN\u20102. Recent evidence suggests that significant amounts of BACE1 and \u03b3\u2010secretase components localize in the cholesterol\u2010rich region of membranes known as lipid rafts, where A\u03b2 production occurs preferentially. In this study, we investigated the effects of oxidative stress on the BACE1 and \u03b3\u2010secretase components in lipid rafts using human neuroblastoma SH\u2010SY5Y cells exposed to ethacrynic acid (EA), a compound that induces cellular glutathione depletion. Following exposure of cells to EA, heme oxygenase\u20101, a marker protein of oxidative stress, was strongly induced. Moreover, treatment with EA resulted in a significant increase in PS1 protein levels, but not those of nicastrin, APH\u20101, PEN\u20102 or BACE1, in both cell lysates and the lipid raft fraction. This increase in PS1 protein expression was prevented by co\u2010treatment with an antioxidant, N\u2010acetylcysteine (NAC). EA additionally induced a significant increase in PS1 mRNA expression, which was inhibited by NAC. Finally, EA treatment was found to promote A\u03b2 secretion from cells expressing Swedish mutant APP. It appears that in our cell culture model, oxidative stress enhances PS1 protein levels in lipid rafts via up\u2010regulation of PS1 transcription, which may constitute the mechanism underlying the oxidative stress\u2010associated promotion of A\u03b2 production. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22271","type":"journal-article","created":{"date-parts":[[2009,11,2]],"date-time":"2009-11-02T22:15:36Z","timestamp":1257200136000},"page":"1137-1145","source":"Crossref","is-referenced-by-count":61,"title":["Oxidative stress up\u2010regulates presenilin 1 in lipid rafts in neuronal 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