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Titolo:
Early glycated albumin, but not advanced glycated albumin, methylglyoxal, or 3-deoxyglucosone increases the expression of PAI-1 in human peritoneal mesothelial cells
Autore:
Mandl-Weber, S; Haslinger, B; Schalkwijk, CG; Sitter, T;
Indirizzi:
Univ Munich, Klinikum Innenstadt, Med Klin, D-80336 Munich, Germany Univ Munich Munich Germany D-80336 dt, Med Klin, D-80336 Munich, Germany Vrije Univ Amsterdam, Acad Hosp, Dept Clin Chem, Amsterdam, Netherlands Vrije Univ Amsterdam Amsterdam Netherlands Chem, Amsterdam, Netherlands
Titolo Testata:
PERITONEAL DIALYSIS INTERNATIONAL
fascicolo: 5, volume: 21, anno: 2001,
pagine: 487 - 494
SICI:
0896-8608(200109/10)21:5<487:EGABNA>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMINOGEN-ACTIVATOR INHIBITOR-1; GLOMERULAR MESANGIAL CELLS; NITRIC-OXIDE SYNTHASE; ENDOTHELIAL-CELLS; END-PRODUCTS; GENE-EXPRESSION; AMADORI ADDUCTS; SERUM-ALBUMIN; MESSENGER-RNA; CAPD PATIENTS;
Keywords:
mesothelial cells; plasminogen activator inhibitor type 1 (PAI-1); fibrinolysis; glycated human serum albumin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Sitter, T Univ Munich, Klinikum Innenstadt, Med Klin, Ziemssenstr 1, D-80336 Munich,Germany Univ Munich Ziemssenstr 1 Munich Germany D-80336 Munich,Germany
Citazione:
S. Mandl-Weber et al., "Early glycated albumin, but not advanced glycated albumin, methylglyoxal, or 3-deoxyglucosone increases the expression of PAI-1 in human peritoneal mesothelial cells", PERIT DIA I, 21(5), 2001, pp. 487-494

Abstract

Objective:The continuous contact of glucose-containing peritoneal dialysis(PD) fluids with the peritoneum results in the intraperitoneal formation of early and advanced glycation end-products. This nonenzymatic glycation ofproteins may cause morphological and functional alterations to the peritoneum, which may contribute to patient dropout from PD therapy. Because fibrinolytic system components have been demonstrated to play an important role in the balance of intraperitoneal generation and degradation of fibrin, we studied the effect of early and advanced glycated human serum albumin, methylglyoxal, and 3-deoxyglucosone on the synthesis of tissue-type plasminogenactivator (WA), as well as its specific inhibitor (PAI-1), in human peritoneal mesothelial cells (HPMC). Methods: Antigen concentrations in the supernatants of cultured HPMC were measured by ELISA. Northern blot analysis was conducted for mRNA expression. Electrophoretic mobility shift assays were applied to demonstrate the involvement of the transcription factors nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1) in signal transduction. Results: Incubation of HPMC with early glycated albumin (GHSA) resulted ina time- and concentration-dependent increase in PAI-1 mRNA expression and antigen secretion. In contrast, no changes in PAI-1 synthesis occurred after stimulation with either the 1,2-dicarbonyl compounds methylglyoxal and 3-deoxyglucosone, or with late advanced glycation end-products. tPA synthesiswas not affected by any of the tested components. Furthermore, HPMC exposed to GHSA induced NF-kappaB and AP-1 DNA binding activity, suggesting that GHSA-induced overexpression of PAI-1 is transcriptionally regulated by bothtranscription factors. Conclusions: We conclude that Amadori modified glycated albumin upregulates PAI-1 synthesis in HPMC, possibly mediated through the activation of the transcription factors NF-kappaB and AP-1. The present data support the clinical relevance of the formation of glycated proteins and their involvement in pathological processes in PD patients. Thus, glycated albumin may contribute to an imbalance between intraperitoneal formation and degradation of fibrin that causes peritoneal structural alterations, with subsequent membrane failure.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 17:06:37