title: Oxidation and turnover of renal metallothioneins after an injection of ferric nitrilotriacetate.
abstract: Metallothioneins (MTs) have demonstrated strong antioxidant properties, however the biological significance of their effect against hydroxyl radical toxicity remains unclear. We investigated the oxidation and turnover of renal MTs in MT-preinduced mice after an injection of ferric nitrilotriacetate (Fe-NTA). Incubation of MTs with Fe-NTA and H(2)O(2) resulted in a loss of their metal-binding properties and a decrease in their thiol concentration independent of binding potential and isoforms. Moreover, in vitro reduction of renal oxidized MT with dithiothreitol (DTT) reversed these oxidative changes. An injection of Fe-NTA oxidized renal preinduced MT in Zn- and Cd-pretreated mice. The metal-binding properties of renal MTs were lost when the Fe-NTA dose was increased. However, analysis of renal MTs using an immunoassay showed that its protein concentration did not decrease 4h after the injection with various Fe-NTA doses. Furthermore, in vitro reduction of renal oxidized MTs with DTT resulted in an increase in the concentration of metals in the MT fraction. These data indicate that radicals produced by Fe-NTA may oxidize MTs in vitro and in vivo. When we investigated the turnover of oxidized MTs in Fe-NTA-treated mice, effects on the concentration of renal (35)S-labeled MTs were opposite to those observed in Cd-pretreated mice. The concentration of preinduced (35)S-labeled MTs in the kidneys of Cd-pretreated mice showed a significant decrease (p<0.05), whereas that of newly synthesized (35)S-labeled MTs showed a considerable increase. These data suggest that degradation of oxidized MTs may be faster than intact MTs. Therefore, the radical scavenging system of MTs may include their induction and degradation during oxidative stress conditions.
authors: Osaka Ohtani University, Tondabayashi, Osaka, Japan. minkyon@osaka-ohtani.ac.jp
authors: Kyong-Son
authors: KS
authors: Min
authors: Naomi
authors: N
authors: Kishi
authors: Nozomu
authors: N
authors: Yamashita
authors: Keiichi
authors: K
authors: Tanaka
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002104:Cadmium / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D051379:Mice; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D015032:Zinc / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005290:Ferric Compounds; D002104:Cadmium; D008668:Metallothionein; D006861:Hydrogen Peroxide; D015032:Zinc; D009571:Nitrilotriacetic Acid; D004229:Dithiothreitol; C020326:ferric nitrilotriacetate