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In this study, we tested whether induction of hypoxia inducible factor\u20101 (HIF\u20101) may exert cytoprotective effects against mitochondrial dysfunction caused by 3\u2010nitropropionic acid (3\u2010NP) in glial cells. Preconditioning of C6 astroglial cells with cobalt chloride, mimosine (MIM), and desferrioxamine (DFO), all of which known to activate HIF\u20101, significantly attenuated cytotoxicity induced by 3\u2010NP, an irreversible inhibitor of mitochondrial complex II, and antimycin A, a mitochondrial complex III inhibitor. Application of cadmium chloride capable of neutralizing cobalt\u2010induced HIF\u20101 activation, HIF\u2010specific oligodeoxynucleotide (ODN) decoy, and antisense phosphorothioate ODN against HIF\u20101\u03b1 abolished the protective effect mediated by preconditioning with cobalt chloride. Preloading of C6 cells with SN50, PD98059, or SB202190, the respective inhibitor of nuclear factor\u2010\u03baB (NF\u2010\u03baB), p44\/p42 extracellular signal\u2010regulated kinase (ERK), and p38 mitogen\u2010activated protein kinase (MAPK), failed to affect the protection afforded by cobalt preconditioning. Taken together, these results suggest that HIF\u20101 induction secondary to preconditioning with cobalt chloride or iron chelators may mediate the protective effects against metabolic insult induced by the mitochondrial inhibitor 3\u2010NP in C6 astroglial cells.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2005.03032.x","type":"journal-article","created":{"date-parts":[[2005,4,13]],"date-time":"2005-04-13T18:47:10Z","timestamp":1113418030000},"page":"513-525","source":"Crossref","is-referenced-by-count":53,"title":["Induction of hypoxia inducible factor\u20101 attenuates metabolic insults induced by 3\u2010nitropropionic acid in rat C6 glioma cells"],"prefix":"10.1111","volume":"93","author":[{"given":"Ya\u2010Ting","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzyh\u2010Chwen","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding\u2010I","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,3,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.9.3767"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(98)00114-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-10-04181.1993"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199706000-00006"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200009)48:3<285::AID-ANA2>3.0.CO;2-8"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200204000-00003"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-13-04668.2001"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.11.5.9141507"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200101000-00005"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01453.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.1057"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.4049\/jimmunol.155.5.2459","article-title":"Activation of nuclear factor\u2010kappa B and gene expression in human endothelial cells by the common haptens nickel and cobalt","volume":"155","author":"Goebeler M.","year":"1995","journal-title":"J. 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