Transcriptional regulation of indoleamine 2,3-dioxygenase (IDO) by tryptophan and its analogue : Down-regulation of the indoleamine 2,3-dioxygenase (IDO) transcription by tryptophan and its analogue
Indoleamine 2,3-dioxygenase (IDO; EC 1.13.11.42) is a rate-limiting enzyme involved in the catabolism of tryptophan, which is an essential amino acid. It is induced under pathological conditions, such as the presence of viral infections or tumour cells. This enzyme is induced by IFN-gamma in the mou...
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Published in | Cytotechnology (Dordrecht) Vol. 54; no. 2; pp. 107 - 113 |
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Main Authors | , , , , , |
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Abstract | Indoleamine 2,3-dioxygenase (IDO; EC 1.13.11.42) is a rate-limiting enzyme involved in the catabolism of tryptophan, which is an essential amino acid. It is induced under pathological conditions, such as the presence of viral infections or tumour cells. This enzyme is induced by IFN-gamma in the mouse rectal carcinoma cell line CMT-93. It is known that both 1-methyl-L: -tryptophan (1-MT) and methylthiohydantoin-DL: -tryptophan (MTH-trp) are tryptophan analogues, and are authentic inhibitors of the enzymatic activity of IDO. In this study, we examined the effects of both 1-MT and MTH-trp on the IFN-gamma inducible IDO expression of CMT-93. As a result, the IFN-gamma inducible IDO mRNA and the protein levels in CMT-93 were suppressed by 1-MT and MTH-trp, independently. Moreover, tryptophan (Trp), as a substrate of IDO, also suppressed IDO induction by IFN-gamma at the transcriptional level. These results suggest that 1-MT and MTH-trp are as inhibitors of IDO enzymatic activity, and Trp suppresses IDO induction by IFN-gamma at the transcriptional level. |
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AbstractList | Indoleamine 2,3-dioxygenase (IDO; EC 1.13.11.42) is a rate-limiting enzyme involved in the catabolism of tryptophan, which is an essential amino acid. It is induced under pathological conditions, such as the presence of viral infections or tumour cells. This enzyme is induced by IFN-γ in the mouse rectal carcinoma cell line CMT-93. It is known that both 1-methyl-
l
-tryptophan (1-MT) and methylthiohydantoin-
dl
-tryptophan (MTH-trp) are tryptophan analogues, and are authentic inhibitors of the enzymatic activity of IDO. In this study, we examined the effects of both 1-MT and MTH-trp on the IFN-γ inducible IDO expression of CMT-93. As a result, the IFN-γ inducible IDO mRNA and the protein levels in CMT-93 were suppressed by 1-MT and MTH-trp, independently. Moreover, tryptophan (Trp), as a substrate of IDO, also suppressed IDO induction by IFN-γ at the transcriptional level. These results suggest that 1-MT and MTH-trp are as inhibitors of IDO enzymatic activity, and Trp suppresses IDO induction by IFN-γ at the transcriptional level. Indoleamine 2,3-dioxygenase (IDO; EC 1.13.11.42) is a rate-limiting enzyme involved in the catabolism of tryptophan, which is an essential amino acid. It is induced under pathological conditions, such as the presence of viral infections or tumour cells. This enzyme is induced by IFN-gamma in the mouse rectal carcinoma cell line CMT-93. It is known that both 1-methyl-L: -tryptophan (1-MT) and methylthiohydantoin-DL: -tryptophan (MTH-trp) are tryptophan analogues, and are authentic inhibitors of the enzymatic activity of IDO. In this study, we examined the effects of both 1-MT and MTH-trp on the IFN-gamma inducible IDO expression of CMT-93. As a result, the IFN-gamma inducible IDO mRNA and the protein levels in CMT-93 were suppressed by 1-MT and MTH-trp, independently. Moreover, tryptophan (Trp), as a substrate of IDO, also suppressed IDO induction by IFN-gamma at the transcriptional level. These results suggest that 1-MT and MTH-trp are as inhibitors of IDO enzymatic activity, and Trp suppresses IDO induction by IFN-gamma at the transcriptional level. |
Author | TONE, Shigenobu MIYAWAKI, Chie OKAMOTO, Takeaki KANOUCHI, Hiroaki ONO, Sayuri MINATOGAWA, Yohsuke |
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Cites_doi | 10.1038/nri1457 10.1016/S0021-9258(17)30447-7 10.1042/bj3550425 10.1096/fasebj.5.11.1907934 10.1084/jem.189.9.1363 10.1002/ijc.10645 10.1038/nm1196 10.1016/0006-291X(92)91590-M 10.1016/S0021-9258(19)77982-4 10.1002/ijc.2910600117 10.1016/S0021-9258(18)53504-3 10.1074/jbc.271.32.19140 10.1006/cyto.1998.0426 10.1016/S0021-9258(17)35696-X 10.1126/science.281.5380.1191 10.1258/0004563011900461 10.1016/0024-3205(87)90149-4 10.1089/jir.1995.15.517 10.1073/pnas.76.9.4350 |
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Keywords | Regulation(control) Transcription Enzyme Analog Tryptophan 1-Methyl-L- tryptophan, Methylthiohydantoin-DL-tryptophan Indoleamine-pyrrole 2,3-dioxygenase Oxidoreductases CMT-93· IFN-γ |
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Snippet | Indoleamine 2,3-dioxygenase (IDO; EC 1.13.11.42) is a rate-limiting enzyme involved in the catabolism of tryptophan, which is an essential amino acid. It is... |
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SubjectTerms | Biological and medical sciences Fundamental and applied biological sciences. Psychology Original Research |
Title | Transcriptional regulation of indoleamine 2,3-dioxygenase (IDO) by tryptophan and its analogue : Down-regulation of the indoleamine 2,3-dioxygenase (IDO) transcription by tryptophan and its analogue |
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