title: Protein nitration promotes inducible nitric oxide synthase transcription mediated by NF-κB in high glucose-stimulated human lens epithelial cells.
abstract: Although an important event in hyperglycaemia-induced oxidative stress is the nuclear factor-kappa b (NF-κB)-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-κB and iNOS, to alter their functions. In this study, we found high glucose caused conspicuous nitration of nuclear NF-κB p65 and its co-activator p300 in human lens epithelial cells. The nitration of NF-κB and p300 promoted their co-localization and binding to ensure the activation of the iNOS gene transcription. Moreover, nearly all predicted NF-κB binding sites in the human iNOS gene promoter were responsive to high glucose stimulation, might for a synergistic role. While, only the NF-κB 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-κB-activated iNOS gene transcription in human lens epithelial cells by high glucose stimulation.
authors: Department of Molecular Biology, Hebei Key Lab of Laboratory Animal, Hebei Medical University, Shijiazhuang, China.
authors: Yanning
authors: Y
authors: Li
authors: Demei
authors: D
authors: Liu
authors: Yuan
authors: Y
authors: Liu
authors: En
authors: E
authors: Li
authors: Hui
authors: H
authors: Wang
authors: Kun
authors: K
authors: Liu
authors: Jinsheng
authors: J
authors: Qi
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D048909:Diabetes Complications; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D018384:Oxidative Stress; D030421:Peroxynitrous Acid / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051996:Transcription Factor RelA / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D051996:Transcription Factor RelA; D030421:Peroxynitrous Acid; D052247:Nitric Oxide Synthase Type II; D050880:p300-CBP Transcription Factors; D005947:Glucose