期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 370, 期 1-2, 页码 78-86出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2013.02.015
关键词
Protein nitration; NF-kappa B; p300; Inducible nitric oxide synthase; Transcriptional control
资金
- Major State Basic Research Development Program of China (973 Program) [2012CB518601]
- National Natural Science Foundation of China [81070658]
- Hebei Natural Science Foundation [C2009001092, H2012206005]
Although an important event in hyperglycaemia-induced oxidative stress is the nuclear factor-kappa b (NF-kappa B)-activated inducible nitric oxide synthase (iNOS) expression, the underlying mechanism is not fully characterized. Peroxynitrite, formed from NO and superoxide, can induce multiple proteins nitration, even including NF-kappa B and iNOS, to alter their functions. In this study, we found high glucose caused conspicuous nitration of nuclear NF-kappa B p65 and its co-activator p300 in human lens epithelial cells. The nitration of NF-kappa B and p300 promoted their co-localization and binding to ensure the activation of the iNOS gene transcription. Moreover, nearly all predicted NF-kappa B binding sites in the human iNOS gene promoter were responsive to high glucose stimulation, might for a synergistic role. While, only the NF-kappa B binding site -5212 showed significant alterations by high glucose and peroxynitrite stimulations, indicating it a more important role in the protein nitration promoted iNOS gene transcription. Our results demonstrated that protein nitration can promote the NF-kappa B-activated iNOS gene transcription in human lens epithelial cells by high glucose stimulation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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