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To approach this issue we examined BDNF release from PC12 cells, a well\u2010established model of neurosecretion, in response to hypoxic stimuli. BDNF secretion from neuronally differentiated PC12 cells was strongly stimulated by exposure to intermittent hypoxia (IH). This response was inhibited by <jats:italic>N<\/jats:italic>\u2010acetyl\u2010<jats:sc>l<\/jats:sc>\u2010cysteine, a potent scavenger of reactive oxygen species (ROS) and mimicked by exogenous ROS. IH\u2010induced BDNF release requires activation of tetrodotoxin sensitive Na<jats:sup>+<\/jats:sup> channels and Ca<jats:sup>2+<\/jats:sup> influx through N\u2010 and L\u2010type channels, as well as mobilization of internal Ca<jats:sup>2+<\/jats:sup> stores. These results demonstrate that oxidative stress can stimulate BDNF release and that underlying mechanisms are similar to those previously described for activity\u2010dependent BDNF secretion from neurons. Surprisingly, we also found that IH\u2010induced secretion of BDNF was blocked by dopamine D<jats:sub>2<\/jats:sub> receptor antagonists or by inhibition of dopamine synthesis with \u03b1\u2010methyl\u2010<jats:italic>p<\/jats:italic>\u2010tyrosine. These data indicate that oxidative stress can stimulate BDNF release through an autocrine or paracrine loop that requires dopamine receptor activation.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2005.03572.x","type":"journal-article","created":{"date-parts":[[2005,12,22]],"date-time":"2005-12-22T15:54:31Z","timestamp":1135266871000},"page":"694-705","source":"Crossref","is-referenced-by-count":57,"title":["Secretion of brain\u2010derived neurotrophic factor from PC12 cells in response to oxidative stress requires autocrine dopamine signaling"],"prefix":"10.1111","volume":"96","author":[{"given":"Hong","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxiang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanduri R.","family":"Prabhakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Boswell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Katz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.20028484"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.63031021.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-19-07417.2000"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"10\u2003399","DOI":"10.1523\/JNEUROSCI.22-23-10399.2002","article-title":"Cellular mechanisms regulating activity\u2010dependent release of native brain\u2010derived neurotrophic factor from hippocampal neurons","volume":"22","author":"Balkowiec A.","year":"2002","journal-title":"J. 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