Methylglyoxal and advanced glycation end-products promote cytokines expression in peritoneal mesothelial cells via MAPK signaling.
Am J Med Sci
; 349(2): 105-9, 2015 Feb.
Article
en En
| MEDLINE
| ID: mdl-25581570
ABSTRACT
BACKGROUND:
Peritoneal dialysis fluid degrades glucose into glucose degradation products that impair peritoneal mesothelial cell functions. These compounds are known to interfere with many cellular functions and to promote the formation of advanced glycation end products (AGEs). This study aimed to investigate the biological effects and the underlying mechanism of glucose degradation products and AGEs on mesothelial cells.METHODS:
Cell proliferation was determined using [3H]-thymidine incorporation assay. Real-time polymerase chain reaction and enzyme linked immunosorbent assay (ELISA) were used to determine the mRNA and protein expression of cytokines. Reactive oxygen species production in mesothelial cells was determined by flow cytometry. Western blot was used to measure the protein expression of p38 MAPK.RESULTS:
Methylglyoxal (MGO) and AGE-human serum albumin (AGE-HSA) inhibited human peritoneal mesothelial cells proliferation in a dose- and time-dependent manner. The mRNA and protein expression of cytokines including vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) was significantly increased after treatment with MGO and AGE-HSA. Also, the antioxidant N-acetylcysteine (NAC) inhibited MGO- or AGE-HSA-induced reactive oxygen species generation. Western blot showed that MGO and AGE increased the phosphorylation levels of p38 MAPK, which was significantly attenuated after treatment of NAC or p38 MAPK inhibitor SB203580. Furthermore, AGE- or MGO-induced increased expression of VEGF and MCP-1 was significantly reduced in the presence of NAC or SB203580.CONCLUSIONS:
Together, this study suggested that AGE or MGO promoted VEGF and MCP-1 expression through activation of p38 MAPK signaling.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Peritoneo
/
Piruvaldehído
/
Regulación de la Expresión Génica
/
Productos Finales de Glicación Avanzada
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Quimiocina CCL2
/
Sistema de Señalización de MAP Quinasas
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Factor A de Crecimiento Endotelial Vascular
Límite:
Humans
Idioma:
En
Revista:
Am J Med Sci
Año:
2015
Tipo del documento:
Article
País de afiliación:
China