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When compared with HI\u2010treated rat pups, 100% O<jats:sub>2<\/jats:sub> resuscitation of HI\u2010treated rat pups increases HI\u2010induced ER Bax levels, ER\u2010mediated cell death signaling, and resultant lesion volume and inflammation due to increased necrotic\u2010like cell death. To better characterize the role of Bax intracellular shuttling ER cell death signaling and necrotic\u2010like cell death, we used rotenone\u2010treated P5 neuronal cortical cultures to increase ER Bax levels and subsequent cell death signaling. We treated P5 primary cortical neurons with 25 \u03bcM and 100 \u03bcM rotenone as an apoptotic or necrotic\u2010like stimulus, respectively, and measured intracellular organelle Bax levels and the subsequent activation of ER\/mitochondrial cell death signaling. The 25 \u03bcM rotenone treatment promptly increased nuclear Bax levels followed by a later increase in mitochondrial Bax levels and caspase\u2010mediated cleavage of \u03b1\u2010fodrin. The 100 \u03bcM rotenone treatment also resulted in an early increase in nuclear Bax levels followed by a subsequent increase in ER Bax levels and calpain\u2010mediated cleavage of \u03b1\u2010fodrin. After pretreatment with the immunosuppressive and neuroprotective FK506, there was a delay in Bax intracellular shifts and cell death signaling for both the 25 and 100 \u03bcM rotenone treatments. These results suggest that the different outcomes of apoptotic\u2010like vs. necrotic\u2010like cell death resulting from the treatment of neuronal cultures with rotenone at 25 and 100\u03bcM rotenone reflect changes in the intracellular trafficking of Bax among different organelles. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22019","type":"journal-article","created":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T18:13:52Z","timestamp":1234894432000},"page":"2047-2065","source":"Crossref","is-referenced-by-count":15,"title":["Bax shuttling after rotenone treatment of neuronal primary cultures: Effects on cell death phenotypes"],"prefix":"10.1002","volume":"87","author":[{"given":"Martin B.","family":"Gill","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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