Nitrosothiol Formation and Protection against Fenton Chemistry by Nitric Oxide-induced Dinitrosyliron Complex Formation from Anoxia-initiated Cellular Chelatable Iron Increase

作者：Li Qian^*; Li Chuanyu; Mahtani Harry K; Du Jian; Patel Aashka R; Lancaster Jack R Jr

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289(29): 19917-19927.

DOI：10.1074/jbc.M114.569764

Dinitrosyliron complexes (DNIC) have been found in a variety of pathological settings associated with (NO)-N-center dot. However, the iron source of cellular DNIC is unknown. Previous studies on this question using prolonged (NO)-N-center dot exposure could be misleading due to the movement of intracellular iron among different sources. We here report that brief (NO)-N-center dot exposure results in only barely detectable DNIC, but levels increase dramatically after 1-2 h of anoxia. This increase is similar quantitatively and temporally with increases in the chelatable iron, and brief (NO)-N-center dot-treatment prevents detection of this anoxia-induced increased chelatable iron by deferoxamine. DNIC formation is so rapid that it is limited by the availability of (NO)-N-center dot and chelatable iron. We utilize this ability to selectively manipulate cellular chelatable iron levels and provide evidence for two cellular functions of endogenous DNIC formation, protection against anoxia-induced reactive oxygen chemistry from the Fenton reaction and formation by transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these high chelatable iron levels are comparable with DNIC levels and suggest that under these conditions, both DNIC and RSNO are the most abundant cellular adducts of (NO)-N-center dot.

• 出版日期2014-7-18
• 单位安徽医科大学