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Tissue-specific activation of mitogen-activated protein kinases for expression of transthyretin by phenylalanine and its metabolite, phenylpyruvic acid

Title
Tissue-specific activation of mitogen-activated protein kinases for expression of transthyretin by phenylalanine and its metabolite, phenylpyruvic acid
Authors
Park J.-W.Lee M.H.Choi J.-O.Park H.-Y.Jung S.-C.
Ewha Authors
박혜영정성철박주원
SCOPUS Author ID
박혜영scopus; 정성철scopus; 박주원scopus
Issue Date
2010
Journal Title
Experimental and Molecular Medicine
ISSN
1226-3613JCR Link
Citation
vol. 42, no. 2, pp. 105 - 115
Indexed
SCI; SCIE; SCOPUS; KCI WOS scopus
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 HNF4α. 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.
DOI
10.3858/emm.2010.42.2.012
Appears in Collections:
의과대학 > 의학과 > Journal papers
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