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- Title
Nitrative and oxidative modifications of enolase are associated with iron in iron-overload rats and in vitro.
- Authors
Lu, Naihao; Li, Xueli; Li, Jinyang; Xu, Wenjing; Li, Hailing; Gao, Zhonghong
- Abstract
Iron overload is one of the most common iron-related toxicities, and liver is the major organ that is injured. Although oxidative stress is well accepted in the pathological mechanism of iron overload, nitrative modification in liver and the role of iron are relatively unknown. In this work, the nitrative and oxidative stress in liver was investigated in an iron-overload rat model. It was found that after 15 weeks of iron dextran administration, consistent with the increase of iron content in rat liver, both protein tyrosine nitration and protein oxidation were clearly elevated. By means of immunoprecipitation analysis, it was found that enolase nitration and oxidation status were significantly increased in iron-overload liver, whereas both α-enolase expression and activity were clearly decreased. The effects of different forms of iron on NaNO-HO- and peroxynitrite (ONOO)-dependent enolase nitration and oxidation were further investigated in vitro to elucidate the possible role of iron in enolase dysfunction in vivo. Compared with EDTA-Fe(III), ferric citrate, and ferritin, heme (hemin and hemoglobin) showed higher efficiency in catalyzing protein nitration in both models. Besides the major contribution of free iron (Fe and Fe) to catalyze protein oxidation, Fe also directly acted as a competitive inhibitor and produced a significant decrease in enzyme activity. These results suggest that the existence of various forms of iron is an important contributing factor to the elevated nitrative/oxidative modifications and diminished activity of α-enolase in the development and progress of iron-overload-associated syndromes.
- Subjects
NITRATION; OXIDATION; ENOLASE; IRON in the body; LABORATORY rats; IRON metabolism disorders; OXIDATIVE stress
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2011, Vol 16, Issue 3, p481
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-010-0747-6