title: The dual effects of nitrite on hemoglobin-dependent redox reactions.
abstract: Evidence to support the role of heme proteins-dependent reactions as major inducers of oxidative damage is increasingly present. Nitrite (NO2(-)) is one of the major end products of NO metabolism, and from the daily consumption. Although the biological significance of heme proteins/NO2(-)-mediated protein tyrosine nitration is a subject of great interest, the important roles of NO2(-) on heme proteins-dependent redox reactions have been greatly underestimated. In this study, we investigated the influence of NO2(-) on met-hemoglobin (Hb)-dependent oxidative and nitrative stress. It was found that NO2(-) effectively reduced cytotoxic ferryl intermediate back to ferric Hb in a biphasic kinetic reaction. However, the presence of NO2(-) surprisingly exerted pro-oxidant effect on Hb-H2O2-induced protein (bovine serum albumin, enolase) oxidation at low concentrations and enhanced the loss of HepG2 cell viability. In the reduction of ferryl Hb to ferric state, NO2(-) was decreased and oxidized to a nitrating agent NO2, Tyr12 and Tyr191 in enolase were subsequently nitrated. In contrast to the frequently inhibitive effect of nitrotyrosine, NO2(-)-triggered tyrosine nitration might play an important role in enolase activation. These data provided novel evidence that the dietary intake and potential therapeutic application of NO2(-) would possess anti- and pro-oxidant activities through interfering in hemoglobin-dependent redox reactions. Besides the classic role in protein tyrosine nitration, the dual effects on hemoglobin-triggered oxidative stress may provide new insights into the physiological and toxicological implications of NO2(-) with heme proteins.
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China; Jiangxi Key Laboratory of Functional Organic Molecules, Jiangxi Science and Technology, Normal University, Nanchang 330013, China. Electronic address: naihaolu@gmail.com.
authors.forename: Naihao
authors.initials: N
authors.lastname: Lu
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: He
authors.affiliation: Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
authors.affiliation: Jiangxi Key Laboratory of Functional Organic Molecules, Jiangxi Science and Technology, Normal University, Nanchang 330013, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China. Electronic address: yiyuanpeng@yahoo.com.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Peng
mesh_terms: D006454:Hemoglobins / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D009573:Nitrites / Q000378:metabolism*; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured
chemical_list: D006454:Hemoglobins; D009573:Nitrites
keywords: Anti-oxidant; Hemoglobin; Nitrite; Oxidative/nitrative stress; Pro-oxidant