Nitrosothiol formation catalyzed by ceruloplasmin. Implication for cytoprotective mechanism in vivo

Katsuhisa Inouet, Takaaki Akaike, Yoichi Miyamoto, Tatsuya Okamoto, Tomohiro Sawa, Masaki Otagiri, Shinnichiro Suzuki, Tetsuhiko Yoshimura, Hiroshi Maeda

研究成果: Article査読

177 被引用数 (Scopus)

抄録

Ceruloplasmin (CP) is a major multicopper-containing plasma protein that is not only involved in iron metabolism through its ferroxidase activity but also functions as an antioxidant. However, physiological substrates for CP have not been fully identified nor has the role of CP been fully understood. The reaction of nitric oxide (NO) with CP was investigated in view of nitrosothiol (RS-NO) formation. First, formation of heavy metal- or CP- catalyzed RS-NO was examined with physiologically relevant concentrations of NO and various thiol compounds (RSH) such as glutathione (GSH). Among the various heavy metal ions and copper-containing enzymes and proteins examined, only copper ion (Cu2+) and CP showed potent RS-NO (S-nitrosoglutathione)- producing activity. Also, RS-NO-forming catalytic activity was evident for CP added exogenously to RAW264 cells expressing inducible NO synthase in culture, but this was not the case for copper ion. Similarly, CP produced endogenously by HepG2 cells showed potent RS-NO-forming activity in the cell culture. One-electron oxidation of NO appears to be operative for RS-NO production via electron transfer from type I copper to a cluster of types 2 and 3 copper in CP. Neurological disorders are associated with aceruloplasminemia; besides RS-NO, S-nitrosoglutathione particularly has been shown to have neuroprotective effect against oxidative stress induced by iron overload. Thus, we suggest that CP plays an important catalytic role in RS-NO formation, which may contribute to its potent antioxidant and cytoprotective activities in vivo in mammalian biological systems.

本文言語English
ページ(範囲)27069-27075
ページ数7
ジャーナルJournal of Biological Chemistry
274
38
DOI
出版ステータスPublished - 1999 9月 17

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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