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To determine whether HO\u20101 induction promotes mitochondrial oxidative stress, assays for 8\u2010<jats:italic>epi<\/jats:italic>PGF<jats:sub>2\u03b1<\/jats:sub> (ELISA), protein carbonyls (ELISA) and 8\u2010OHdG (HPLC\u2010EC) were used to quantify oxidative damage to lipids, proteins, and nucleic acids, respectively, in mitochondrial fractions and whole\u2010cell compartments derived from cultured rat astroglia engineered to over\u2010express human (h) HO\u20101 by transient transfection. Cell viability was assessed by trypan blue exclusion and the MTT assay, and cell proliferation was determined by [<jats:sup>3<\/jats:sup>H] thymidine incorporation and total cell counts. In rat astrocytes, hHO\u20101 over\u2010expression (\u00d73 days) resulted in significant oxidative damage to mitochondrial lipids, proteins, and nucleic acids, partial growth arrest, and increased cell death. These effects were attenuated by incubation with 1 \u00b5M tin mesoporphyrin, a competitive HO inhibitor, or the iron chelator, deferoxamine. Up\u2010regulation of HO\u20101 engenders oxidative mitochondrial injury in cultured rat astroglia. Heme\u2010derived ferrous iron and carbon monoxide (CO) may mediate the oxidative modification of mitochondrial lipids, proteins and nucleic acids in these cells. Glial HO\u20101 hyperactivity may contribute to cellular oxidative stress, pathological iron deposition, and bioenergetic failure characteristic of degenerating and inflamed neural tissues and may constitute a rational target for therapeutic intervention in these conditions. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.20509","type":"journal-article","created":{"date-parts":[[2005,10,12]],"date-time":"2005-10-12T22:17:20Z","timestamp":1129155440000},"page":"655-663","source":"Crossref","is-referenced-by-count":98,"title":["Over\u2010expression of heme oxygenase\u20101 promotes oxidative mitochondrial damage in rat 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