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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
- 박혜영; 정성철; 박주원
- SCOPUS Author ID
- 박혜영; 정성철; 박주원
- Issue Date
- 2010
- Journal Title
- Experimental and Molecular Medicine
- ISSN
- 1226-3613
- Citation
- Experimental and Molecular Medicine vol. 42, no. 2, pp. 105 - 115
- Indexed
- SCI; SCIE; SCOPUS; KCI
- Document Type
- Article
- 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
- Files in This Item:
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Tissue-specific activation of mitogen-activated protein kinases for expression of transthyretin by phenylalanine and its metabolite, phenylpyruvic acid.pdf(1.04 MB)
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