Disease relevance of Tdo2

• These genetic elements were the rat tryptophan oxygenase (TOase) gene promoter, which is active in vivo only in hepatocytes, and the long terminal repeat of the mouse mammary tumor virus (MMTV-LTR) [1].
• This result is in agreement with a significantly higher activity of hepatic tryptophan pyrrolase in mice with melanoma [2].
• Tryptophan oxygenase in the liver and Albert hepatoma in mice [3].

Psychiatry related information on Tdo2

• Crossbred CC57BR/Mv mice inherited tryptophan oxygenase gene and predisposition to alcohol consumption from parent BALB/c and C57BL mice, respectively [4].

High impact information on Tdo2

• A short sequence homology in an equivalent position relative to the cap site was detected between TAT and tryptophan oxygenase, another glucocorticoid-controlled gene from rat liver [5].
• Furthermore, real-time RT-PCR demonstrated an increased expression of tyrosine amino transferase and tryptophan oxygenase mRNA, and transmission electron microscopy confirmed that co-cultured cells produced mature hepatocytes [6].
• Maturation of fetal hepatocytes in vitro by extracellular matrices and oncostatin M: induction of tryptophan oxygenase [7].
• Indoleamine 2,3-dioxgyenase (IDO) is a cytosolic heme protein which, together with the hepatic enzyme tryptophan 2,3-dioxygenase, catalyzes the first and rate-limiting step in the major pathway of tryptophan metabolism, the kynurenine pathway [8].
• The expression of mRNAs encoding tyrosine amino transferase, tryptophan 2,3-dioxygenase, and glucose-6-phosphatase were only detected following coculture with Thy1-positive cells [9].

Biological context of Tdo2

• On the contrary, the early tryptophan-degrading activity was due to gene expression of tryptophan 2,3-dioxygenase (TDO), as shown by Northern and Western analysis [10].
• We isolated a cDNA for tryptophan 2,3-dioxygenase (TDO), another key catabolizing enzyme of tryptophan, from a mouse uterus cDNA library enriched with pregnancy-induced genes [11].

Anatomical context of Tdo2

• In addition, TDO sequences were found in RNA derived from rat brainstem, cerebellum, cortex, hypothalamus, and the remainder of the brain [12].
• However, under such conditions, fetal hepatic cells failed to express genes for adult liver-specific enzymes, such as tryptophan oxygenase (TO) [7].
• These findings demonstrated that TDO is induced in the endometrial stromal cells concomitant with decidualization and suggested its involvement in the implantation process by regulating the tryptophan level at the implantation site [11].
• In the epididymis, TDO protein expression has been found in a totally different cell type in the smooth muscle layer surrounding the epididymal tubules [13].
• Induction of tryptophan 2,3-dioxygenase in the mouse endometrium during implantation [11].

Associations of Tdo2 with chemical compounds

• Identical sequences were obtained when mouse whole brain and liver RNAs were amplified, and these sequences were shown to be 96% identical to the published rat liver tryptophan TDO cDNA sequence [12].
• Lead caused an increase in delta-aminolevulinic acid levels in plasma (> 30-fold) and a decrease in the heme saturation of hepatic tryptophan-2,3-dioxygenase (15 +/- 4% versus 33 +/- 6% of heme saturation in controls; p < 0.001), which is consistent with an effective inhibition of heme synthesis and depletion of the free heme pool [14].
• Liver tryptophan pyrrolase. A major determinant of the lower brain 5-hydroxytryptamine concentration in alcohol-preferring C57BL mice [15].
• A selective and potent inhibitor of hepatic tryptophan 2,3-dioxygenase, 540C91 [(E)-3-[2-(4'-pyridyl)-vinyl]-1H-indole], largely prevented the elevation in mouse brain quinolinic acid resulting from parenteral injection of tryptophan (TRP) [16].
• On the contrary, tryptophan dioxygenase (TDO), a sister enzyme of IDO, is weakly and uniformly expressed in mouse epididymis and, in contrast to IDO, is also expressed in testis [13].

Regulatory relationships of Tdo2

• Tryptophan pyrrolase was also inhibited 4-HP seemed to penetrate into the brain as judged by inhibition of brain catalase activity [17].
• Tryptophan oxygenase activity in alcohol-preferring C57Bl mice and control CBA and DBA/2 mice was studied under nonstressful conditions and after glucocorticoid-induced stress [18].

Other interactions of Tdo2

• Expression of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase in early concepti [10].
• However, there were no significant changes in activities of heme pool associated enzymes, such as catalase, tryptophan pyrrolase and d-aminolevulinic acid synthase in these mice [19].
• Finally, injection of tryptophan and cycloheximide blocked the tryptophan-2,3-dioxygenase response while the tryptophan hydroxylase response was unaltered in both control and TD diet mice [20].
• Under these conditions the enzymatic activity of the kynureninase is decreased and the activity of the kynurenine aminotransferase as well as of the tryptophan pyrrolase is not altered [21].
• The total excretion of the metabolites was significantly higher in the strain of albino N.C.L. than in Swiss albino mice, in accordance with the higher activity of tryptophan pyrrolase, which was present only as holoenzyme [22].

Analytical, diagnostic and therapeutic context of Tdo2

• Assay of tryptophan 2,3-dioxygenase using liver slices and high-performance liquid chromatography [23].
• Northern blot and in situ hybridization analyses demonstrated that the TDO mRNA was induced in the decidualized stromal cells around the implanted embryo at the time of implantation [11].
• TDO mRNA was induced by deciduoma formation as well as embryo transfer but not by ovarian steroid hormones [11].
• However, little is known about the induction of IDO in liver allografts, although a gene specific for tryptophan 2,3-dioxygenase (TDO) is believed to be expressed in the liver [24].
• Beta-glucuronidase, pH and tryptophanase were significantly inhibited after treatment of 0.5% and 1.5% SKTK, while urease was significantly reduced only during and after treatment of 1.5% SKTK as compared with control data [25].

References