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- Title
Glycosylated human oxyhaemoglobin activates nuclear factor-?B and activator protein-1 in cultured human aortic smooth muscle.
- Authors
Peiró, Concepción; Matesanz, Nuria; Nevado, Julián; Lafuente, Nuria; Cercas, Elena; Azcutia, Verónica; Vallejo, Susana; Rodriacute;guez-Mañas, Leocadio; Sánchez-Ferrer, Carlos F.
- Abstract
1: Diabetic vessels undergo structural changes that are linked to a high incidence of cardiovascular diseases. Reactive oxygen species (ROS) mediate cell signalling in the vasculature, where they can promote cell growth and activate redox-regulated transcription factors, like activator protein-1 (AP-1) or nuclear factor-?B (NF-?B), which are involved in remodelling and inflammation processes. Amadori adducts, formed through nonenzymatic glycosylation, can contribute to ROS formation in diabetes. 2: In this study, we analysed whether Amadori-modified human oxyhaemoglobin, glycosylated at either normal (N-Hb) or elevated (E-Hb) levels, can induce cell growth and activate AP-1 and NF-?B in cultured human aortic smooth muscle cells (HASMC). 3: E-Hb (1?nM-1?µM), but not N-Hb, promoted a concentration-dependent increase in cell size from nanomolar concentrations, although it failed to stimulate HASMC proliferation. At 10?nM, E-Hb stimulated both AP-1 and NF-?B activity, as assessed by transient transfection, electromobility shift assays or immunofluorescence staining. The effects of E-Hb resembled those of the proinflammatory cytokine tumour necrosis factor-a (TNF-a). E-Hb enhanced intracellular superoxide anions content and its effects on HASMC were abolished by different ROS scavengers. 4: In conclusion, E-Hb stimulates growth and activates AP-1 and NF-?B in human vascular smooth muscle by redox-sensitive pathways, thus suggesting a possible direct role for Amadori adducts in diabetic vasculopathy.British Journal of Pharmacology (2003); 140, 681-690. doi:10.1038/sj.bjp.0705483
- Subjects
REACTIVE oxygen species; VASCULAR smooth muscle; CARDIOVASCULAR diseases; TRANSCRIPTION factors; GROWTH factors; OXYHEMOGLOBIN
- Publication
British Journal of Pharmacology, 2003, Vol 140, Issue 4, p681
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0705483