RT Journal Article
T1 Amadori adducts activate nuclear factor-kB-related proinflammatory genes in cultured human peritoneal mesothelial cells
A1 Nevado Blanco, Julián
A1 Peiró Vallejo, Concepción
A1 Vallejo, Susana
A1 El-Assar, Mariam
A1 Lafuente Gómez, Nuria
A1 Matesanz, Nuria
A1 Azcutia Criado, Verónica
A1 Cercas Alonso, Elena
A1 Sánchez Ferrer, Carlos Félix
A1 Rodríguez Mañas, Leocadio
AB 1 Diabetes mellitus leads to a high incidence of several so-called complications, sharing similar pathophysiological features in several territories. Previous reports points at early nonenzymatic glycosylation products (Amadori adducts) as mediators of diabetic vascular complications. In the present study, we analysed a possible role for Amadori adducts as stimulators of proinflammatory pathways in human peritoneal mesothelial cells (HPMCs). 2 Cultured HPMCs isolated from 13 different patients (mean age 38.7+/-16 years) were exposed to different Amadori adducts, that is, highly glycated haemoglobin (10 nM) and glycated bovine serum albumin (0.25 mg/ml-1), as well as to their respective low glycosylation controls. Amadori adducts, but not their respective controls, elicited a marked increase of NF-kB activation, as determined by electromobility shift assays and transient transfection experiments. 3 Additionally, Amadori adducts significantly increased the production of NF-kB-related proinflammatory molecules, including cytokines, such as TNF-alpha, IL-1beta or IL-6, and enzymes, such as cyclooxygenase-2 and inducible nitric oxide (NO) synthase, this latter leading to the release of NO by HPMCs.4 The effects of Amadori adducts were mediated by different reactive oxygen and nitrosative species (e.g. superoxide anions, hydroxyl radicals, and peroxynitrite), as they were blunted by coincubation with the appropriate scavengers. Furthermore, NO generated upon exposure to Amadori adducts further stimulated NF-kB activation, either directly or after combination with superoxide anions to form peroxynitrite.5 We conclude that Amadori adducts can favour peritoneal inflammation by exacerbating changes in NO synthesis pathway and triggering NF-kB-related proinflammatory signals in human mesothelial cells.
PB Wiley
YR 2005
FD 2005-07-04
LK https://hdl.handle.net/20.500.14352/100798
UL https://hdl.handle.net/20.500.14352/100798
LA eng
NO Nevado, Julián, et al. «Amadori Adducts Activate Nuclear Factor‐ κ B‐related Proinflammatory Genes in Cultured Human Peritoneal Mesothelial Cells». British Journal of Pharmacology, vol. 146, n.o 2, septiembre de 2005, pp. 268-79. DOI.org (Crossref), https://doi.org/10.1038/sj.bjp.0706309.
NO Fondo de Investigaciones Sanitarias
NO Comunidad de Madrid
NO Ministerio de Educación y Ciencia (España)
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 24 abr 2025