Tissue-specific activation of mitogen-activated protein kinases for expression of transthyretin by phenylalanine and its metabolite, phenylpyruvic acid
Experimental & Molecular Medicine
;
: 105-115, 2010.
Artículo
en Inglés
| WPRIM
| ID: wpr-81944
ABSTRACT
Phenylketonuria is an autosomal recessive disorder caused by a deficiency of phenylalanine hydroxylase. Transthyretin has been implicated as an indicator of nutritional status in phenylketonuria patients. In this study, we report that phenylalanine and its metabolite, phenylpyruvic acid, affect MAPK, changing transthyretin expression in a cell- and tissue-specific manner. Treatment of HepG2 cells with phenylalanine or phenylpyruvic acid decreased transcription of the TTR gene and decreased the transcriptional activity of the TTR promoter site, which was partly mediated through HNF4alpha. Decreased levels of p38 MAPK were detected in the liver of phenylketonuria-affected mice compared with wild-type mice. In contrast, treatment with phenylalanine increased transthyretin expression and induced ERK1/2 activation in PC-12 cells; ERK1/2 activation was also elevated in the brainstem of phenylketonuria-affected mice. These findings may explain between-tissue differences in gene expression, including Ttr gene expression, in the phenylketonuria mouse model.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Especificidad de Órganos
/
Fenilalanina Hidroxilasa
/
Ácidos Fenilpirúvicos
/
Fenilalanina
/
Fenilcetonurias
/
Tronco Encefálico
/
Prealbúmina
/
Regulación de la Expresión Génica
/
Proteína Quinasa 3 Activada por Mitógenos
/
Proteínas Quinasas p38 Activadas por Mitógenos
Tipo de estudio:
Estudio pronóstico
Límite:
Animales
/
Humanos
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2010
Tipo del documento:
Artículo
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