Disease relevance of Tdo2

• Tryptophan 2,3-dioxygenase mRNA was measured in a Krebs ascites cell-free protein synthesizing system supplemented with rabbit reticulocyte initiation factors [1].
• However, tryptophan oxygenase was not responsive to glucocorticoids in hepatoma 7800 although receptor levels were quite high, and there were no indications that the receptor molecules were altered [2].
• Pretranslational control of tryptophan oxygenase levels in Morris hepatoma and host liver [3].
• Chronic administration of pyrazole in the diet of rats does not cause toxicity and prevents the chronic effects of ethanol on: (1) the redox states of the hepatic NAD(P) couples; (2) liver tryptophan pyrrolase activity; (3) brain tryptophan and 5-hydroxytryptamine metabolism [4].
• Hypoxic rats also showed evidence of tissue hypoxia; liver tryptophan oxygenase levels were increased to 21 +/- 2 nmole/min/mg protein [5].

Psychiatry related information on Tdo2

• Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential association with Tourette syndrome, substance abuse and other disorders [6].
• Changes in tryptophan pyrrolase activity during sleep deprivation were demonstrated to be mediated by the pituitary-adrenal axis [7].

High impact information on Tdo2

• Liver tryptophan pyrrolase activity and metabolism of brain 5-HT in rat [8].
• Finally, the availability of hepatic heme for formation of hemoproteins was deemed to be satisfactory in cirrhotic liver because tryptophan pyrrolase saturation was comparable with controls, and also because heme administered in vivo did not enhance hepatic clearance of the cytochrome P450 substrate antipyrine [9].
• Tissue-specific DNaseI hypersensitive sites in the 5'-flanking sequences of the tryptophan oxygenase and the tyrosine aminotransferase genes [10].
• Tryptophan 2,3-dioxygenase [EC 1.13.11.11; L-tryptophan:oxygen 2,3-oxidoreductase (decyclizing)] activity is induced by glucocorticoid hormones and superinduced by actinomycin D [1].
• Tryptophan 2,3-dioxygenase (EC 1.13.1.12) is a hemoprotein which catalyzes the first step in the oxidative degradation of tryptophan [11].

Chemical compound and disease context of Tdo2

• The results show that the dose-response for decreased TdO and PEPCK activity and elevated serum tryptophan levels are similar if not the same as the dose-response for subchronic retardation of body weight increase [12].
• After decapitation the plasma corticosterone level and the activity of tyrosine aminotransferase and tryptophan pyrrolase in the liver was determined [13].
• The effect of intraperitoneal administration of phenobarbital (80 mg kg-1 body weight) and tryptophan (200 mg kg-1 body weight), separately or in combination, on the microsomal content of cytochrome P-450 and the activity of tryptophan 2,3-dioxygenase (EC 1.13.11.11) in Wistar rat liver was determined at different time intervals after injection [14].
• Bilateral adrenalectomy inhibited the increase in liver tyrosine aminotransferase and tryptophan pyrrolase activity after s.c. administration of cca 50 micrograms 17-beta-estradiol (Agofollin SPOFA, Praha) per 1 kg body weight daily for 14 days [15].
• Induction of heme oxygenase induced by CoCl(2) was not blocked by alpha-tocopherol, but this antioxidant normalized the increase in the level of hemolysis products in the serum and decrease in tryptophan-2,3-dioxygenase holoenzyme activity and cytochrome P450 content [16].

Biological context of Tdo2

• The complete amino acid sequence of the tryptophan 2,3-dioxygenase (TO) of rat liver was determined from the nucleotide sequence of a full length TO cDNA isolated from a rat liver cDNA library and determined its primary structure [17].
• A nucleotide sequence (3.2 kb) of a DNA region located approximately between introns 4 and 7 of the rat tryptophan oxygenase gene was determined [18].
• In the nicotinamide-treated hepatocytes, albumin and tryptophan 2,3-dioxygenase mRNAs were present at much higher levels than in the untreated control, and the inducibility of tryptophan oxygenase gene expression by dexamethasone and glucagon was also preserved [19].
• For study of hormonal regulation of gene expression of tryptophan 2,3-dioxygenase (EC 1. 13. 11. 11, TO), a DNA clone containing a sequence complementary to TO mRNA was prepared with TO mRNA from rat liver enriched 62-fold by immunoadsorption [20].
• Rat liver poly(A+) RNA was separated on a formaldehyde gel, blotted to nitrocellulose, and hybridized to a nick-translated tryptophan oxygenase cDNA clone to analyze the kinetics of tryptophan oxygenase mRNA accumulation [21].

Anatomical context of Tdo2

• Multihormonal regulation of transcription of the tryptophan 2,3-dioxygenase gene in primary cultures of adult rat hepatocytes with special reference to the presence of a transcriptional protein mediating the action of glucocorticoids [20].
• In adrenalectomized rats, the activity of tryptophan oxygenase in liver cytosol was increased 4 h after dexamethasone injection, with a peak on day 2 [22].
• Tryptophan 2,3-dioxygenase in chick embryo hepatocytes: studies in ovo and in culture [23].
• Involvement of lysosomes in substrate stabilization of tryptophan-2,3-dioxygenase in rat liver [24].
• The increased amounts of indican in the urine, and of indole in the cecum arose from accumulation of protein and tryptophan in the cecum rather than an increase in the enzyme tryptophanase which metabolizes tryptophan to indole [25].

Associations of Tdo2 with chemical compounds

• We concluded, contrary to previous reports, that induction of tryptophan pyrrolase definitely will increase the rate of tryptophan breakdown [26].
• Twenty-one-day-old animals which were adrenalectomized on the 10th day, and thus possess no demonstrable enzymatic activity, could respond to cortisol treatment with an elevation of tryptophan oxygenase activity [27].
• However, the alpha-adrenergic effect was different from that of insulin in that, unlike the latter, the inductions of tryptophan oxygenase and tyrosine amino-transferase by dexamethasone alone were not inhibited [28].
• Tryptophan pyrrolase activity (total, holo-, and apoenzyme) was elevated about 2.5-fold in STZ diabetic rats [29].
• Isoproterenol or epinephrine plus phenoxybenzamine induced tryptophan oxygenase and tyrosine aminotransferase [28].

Regulatory relationships of Tdo2

• Therefore, dexamethasone alone or together with glucagon stimulated transcription of tryptophan 2,3-dioxygenase increasing its mRNA and enzyme synthesis in hepatocytes [30].

Other interactions of Tdo2

• Nucleotide sequence of a fragment of the rat tryptophan oxygenase gene showing high affinity to glucocorticoid receptor in vitro [18].
• Induction of hepatic HO-1 mRNA and rapid suppression of ALAS-N mRNA were likely the result of a rapid increase in hepatic free heme concentration as judged by the increase in heme saturation of tryptophan pyrrolase [31].
• BACKGROUND: AND AIM: We recently reported that primary rat hepatocytes treated with 3-acetylpyridine (3-AP), an analog of nicotinic acid, could maintain hepatic differentiated functions such as albumin, tryptophan 2,3-dioxygenase, and connexin 32 (Cx32) mRNA expressions for more than a week [32].
• In the liver of rats exposed to trichloroethylene, cytochrome P-450 concentration and heme saturation of tryptophan pyrrolase (EC 1.13.11.11) are reduced; in addition, the activity of delta-aminolevulinate synthase (EC 2.3.1.37) increased [33].
• Insulin and glucagon as a new regulator system for tryptophan oxygenase activity demonstrated in primary cultured rat hepatocytes [34].

Analytical, diagnostic and therapeutic context of Tdo2

• No increase in total hepatic mRNA levels or tryptophan oxygenase mRNA was found after treatment with these protein synthesis inhibitors [35].
• Thus, there was a good correlation between the dexamethasone receptor level and the induction of tryptophan oxygenase, but there was a dissociation between the receptor level and the induction of tyrosine aminotransferase after adrenalectomy and partial hepatectomy [22].
• In adrenalectomized, 70% hepatectomized rats, tryptophan oxygenase activity decreased significantly during the period of DNA synthesis after partial hepatectomy; it then increased to above the level existing before hepatectomy, reaching a maximum on day 5, and subsequently returned to the level before hepatectomy [22].
• 2 Basal liver tryptophan pyrrolase activity was inhibited by paroxetine in vitro and after oral administration [36].
• The effect of pretreatment of the rat with hydrocortisone or allopurinol was also examined, together with the effects of these treatments on liver tryptophan pyrrolase activity measured in vitro at the beginning and end of perfusion [37].

References