| Autor: |
Vanacore, Roberto M., Eskew, Jeffrey D., Morales, Pedro J., Sung, Lokman, Smith, Ann |
| Zdroj: |
Antioxidants and Redox Signaling; Winter 2000, Vol. 2 Issue: 4 p739-752, 14p |
| Abstrakt: |
ABSTRACTHemehemopexin (210 M) is used as a model for intravenous heme released in trauma, stroke, and ischemia-reperfusion. A transient increase in cellular protein oxidation occurs during receptor-mediated heme transport from hemopexin which is inhibited by the nonpermeable Cu(I) chelator, bathocuproinedisulfonate. Thus, participation of surface redox process involving Cu(I) generation are proposed to be linked to the induction of the protective proteins heme oxygenase-1 (HO-1) and metallothionein-1 (MT-1) by hemehemopexin. The region (153 to 42) in the proximal promoter of the mouse MT-1 gene responds to heme and CoPPhemopexin in transient transfection assays and contains metal-responsive elements for MTF-1 and an antioxidant-responsive element (ARE) overlapping a GC-rich E-box to which USF-1 and -2 bind. No decreases in DNA binding of the diamide-oxidation sensitive USF-1 and -2 occur upon exposure of cells to hemehemopexin. MTF-1 and the ARE-binding proteins are relatively resistant to diamide oxidation and are induced approximately eight- and two-fold, respectively, by hemehemopexin. BCDS prevents the nuclear translocation of MTF-1 by both heme- and CoPPhemopexin complexes as well as MT-1 mRNA induction by CoPPhemopexin. Thus, copper is needed for the surface oxidation events and yet the nuclear translocation of MTF-1 in response to hemopexin occurs via copper, probably Cu(I), -dependent signaling cascades from the hemopexin receptor rather than the oxidation per se. |
| Databáze: |
Supplemental Index |
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