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Increased proteins included lipocortin-5, calgizzarin, ezrin, and transferrin, whereas the decreased proteins were \u03b1<jats:sub>2u<\/jats:sub>-globulin PGCL1, eukaryotic translation elongation factor 1\u03b1<jats:sub>2<\/jats:sub>, and Cu\/Zn superoxide dismutase (SOD1). Among these proteins, we focused on Cu\/Zn-SOD, a crucial antioxidant. Western blot analysis and real-time quantitative PCR analysis confirmed the downregulation of Cu\/Zn-SOD in the chronic hypoxic kidney. Furthermore, our laser capture microdissection system showed that the expression of Cu\/Zn-SOD was predominant in the tubulointerstitium and was decreased by chronic hypoxia. The tubulointerstitial injury estimated by histology and immunohistochemical markers was ameliorated by tempol, a SOD mimetic. This amelioration was associated with a decrease in levels of the oxidative stress markers 4-hydroxyl-2-nonenal and nitrotyrosine. Our in vitro studies utilizing cultured tubular cells revealed a role of TNF-\u03b1 in downregulation of Cu\/Zn-SOD. Since the administration of anti-TNF-\u03b1 antibody ameliorated Cu\/Zn-SOD suppression, TNF-\u03b1 seems to be one of the suppressants of Cu\/Zn-SOD. In conclusion, our proteomic analysis revealed a decrease in Cu\/Zn-SOD, at least partly by TNF-\u03b1, in the chronic hypoxic kidney. This study, for the first time, uncovered maladaptive suppression of Cu\/Zn-SOD as a mediator of a vicious cycle of oxidative stress and subsequent renal injury induced by chronic hypoxia.<\/jats:p>","DOI":"10.1152\/ajprenal.00113.2007","type":"journal-article","created":{"date-parts":[[2007,10,24]],"date-time":"2007-10-24T23:11:57Z","timestamp":1193267517000},"page":"F62-F72","source":"Crossref","is-referenced-by-count":36,"title":["Chronic hypoxia aggravates renal injury via suppression of Cu\/Zn-SOD: a proteomic analysis"],"prefix":"10.1152","volume":"294","author":[{"given":"Daisuke","family":"Son","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Inagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiro","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaomi","family":"Nangaku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.05.014"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Asayama K, Burr IM.Rat superoxide dismutases. 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