| RRC ID |
45364
|
| 著者 |
Sanayama Y, Matsumoto A, Shimojo N, Kohno Y, Nakaya H.
|
| タイトル |
Phenylalanine sensitive K562-D cells for the analysis of the biochemical impact of excess amino acid.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Although it is recognized that the abnormal accumulation of amino acid is a cause of the symptoms in metabolic disease such as phenylketonuria (PKU), the relationship between disease severity and serum amino acid levels is not well understood due to the lack of experimental model. Here, we present a novel in vitro cellular model using K562-D cells that proliferate slowly in the presence of excessive amount of phenylalanine within the clinically observed range, but not phenylpyruvate. The increased expression of the L-type amino acid transporter (LAT2) and its adapter protein 4F2 heavy chain appeared to be responsible for the higher sensitivity to phenylalanine in K562-D cells. Supplementation with valine over phenylalanine effectively restored cell proliferation, although other amino acids did not improve K562-D cell proliferation over phenylalanine. Biochemical analysis revealed mammalian target of rapamycin complex (mTORC) as a terminal target of phenylalanine in K562-D cell proliferation, and supplementation of valine restored mTORC1 activity. Our results show that K562-D cell can be a potent tool for the investigation of PKU at the molecular level and to explore new therapeutic approaches to the disease.
|
| 巻・号 |
4
|
| ページ |
6941
|
| 公開日 |
2014-11-6
|
| DOI |
10.1038/srep06941
|
| PII |
srep06941
|
| PMID |
25373594
|
| PMC |
PMC4221789
|
| MeSH |
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Biological Transport
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Fusion Regulatory Protein-1 / genetics
Fusion Regulatory Protein-1 / metabolism
Gene Expression Regulation
Hemin / pharmacology
Humans
K562 Cells
Mechanistic Target of Rapamycin Complex 1
Models, Biological*
Multiprotein Complexes / genetics
Multiprotein Complexes / metabolism
Phenylalanine / metabolism*
Phenylalanine / pharmacology
Phenylketonurias / genetics
Phenylketonurias / metabolism
Phenylketonurias / pathology
Phenylpyruvic Acids / metabolism
Phenylpyruvic Acids / pharmacology
Signal Transduction
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / metabolism
Valine / metabolism
Valine / pharmacology
|
| IF |
3.998
|
| 引用数 |
4
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
K562(RCB1897)
T24(RCB0431) |
