TAILIEUCHUNG - Báo cáo khoa học: Modulation of nitric oxide-mediated metal release from metallothionein by the redox state of glutathione in vitro

Metallothioneins (MTs) release boundmetalswhen exposed to nitric oxide. At inflammatory sites, both metallothionein and inducible nitric oxide synthase (iNOS) are induced by the same factors and the zinc released from metallothionein by NO suppresses both the induction and activity of iNOS. In a search for a possible modulatory mechanism of this coexpression of counteracting proteins, we investigated the role of the glutathione redox statein vitro because the oxi-dation state of thiols is involved in themetal binding inCd-S or Zn-Sclusters found in metallothioneins, and NO also binds to reduced glutathione via S-nitrosation | Eur. J. Biochem. 271 2408-2416 2004 FEBS fi iiU doi Modulation of nitric oxide-mediated metal release from metallothionein by the redox state of glutathione in vitro Leila Khatai1 Walter Goessler2 Helena Lorencova2 and Klaus Zangger1 1 Institute of Chemistry Organic and Bioorganic Chemistry University of Graz Austria .Institute of Chemistry Analytical Chemistry University of Graz Austria Metallothioneins MTs release bound metals when exposed to nitric oxide. At inflammatory sites both metallothionein and inducible nitric oxide synthase iNOS are induced by the same factors and the zinc released from metallothionein by NO suppresses both the induction and activity of iNOS. In a search for a possible modulatory mechanism of this coexpression of counteracting proteins we investigated the role of the glutathione redox state in vitro because the oxidation state of thiols is involved in the metal binding in Cd-S or Zn-S clutters found in melallolhioneins. and NO dso binds to reduced glutathione via S-nitrosation. Using a variety of techniques we found that NO and also ONOO--mediated metal release from purified MTs is suppressed by reduced glutathione GSH but not by oxidized glutathione. Considering the millimolar concentrations of GSH present in mammalian cells the metal release from MTs by NO should play no role in living systems. Therefore the fact that it has been observed in vivo points to a hitherto unknown mechanism or additional compound s being involved in this physiologically relevant reaction and as long as this additional factor is not found experimental results on the MT-NO interaction should be treated with caution. Contrary to the peroxynitrite-induced activation of guanylyl cyclase where GSH is needed we found that the metal release from metallothionein by peroxynitrite is not enhanced but also suppressed by reduced glutathione. In addition we show that zinc the ma or natural metal ligand in mammalian MTs and suppressor of .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• medical knowledge
• cytoplasm
• analysis of cytoplasmic
• medical research
• oxidation
• Crystal structure
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine