Disease relevance of Tkt

• Our data suggest that TKT deficiency may have clinical significance in humans and raise the possibility that obesity may be treated by partial inhibition of TKT in adipose tissue [1].
• A third subset of NK cells, termed T killer (TK) cells deriving from cultures of conventional but not nude mouse spleens, mediated spontaneous cytotoxicity of P815 mastocytoma cells, but not of virus-infected targets [2].
• B2 cells infected with UV-HSV or transfected with the HSV-1 TK gene and maintained in TK-selective medium showed discrete colonies of cells which displayed a normal flat appearance and expressed the viral TK enzyme [3].
• The TK coding sequence in the cloned fragment has been localized and a smaller recombinant plasmid, pAG0, also carrying an active TK gene, has been constructed to serve as a more convenient vector for transfer, into TK- cells, of genes previously cloned in E. coli [4].
• Using monoclonal antibodies, we previously detected two forms of transformation-associated proteins (TAPs), P64 and P68, in the rat kidney (6m2) cells transformed by the temperature-sensitive 110-murine sarcoma virus-Moloney-mutant [5].

High impact information on Tkt

• Assays capable of distinguishing between foreign and native TK indicated that at least one of the fetuses with the HSV tk gene had some TK enzyme of the HSV type and, therefore, at least one gene copy that was being accurately transcribed and translated to produce a functional protein, despite the absence of selective pressure [6].
• Transketolase haploinsufficiency reduces adipose tissue and female fertility in mice [1].
• No phenotype was observed in the TKT(+/-) cornea, where TKT is especially abundant in wild-type mice [1].
• Other TKT(+/-) tissues had moderate ( approximately 33%; liver, gonads) or relatively little ( approximately 7 to 18%; eye, kidney, heart, brain) reductions in mass [1].
• In MBP-TK transgenic mice, oligodendrocyte ablation was selectively induced by FIAU treatment before and during the onset of myelination [7].

Chemical compound and disease context of Tkt

• Thus, transketolase enzyme and thiamine clearly determine cell proliferation in the Ehrlich's ascites tumour model [8].
• Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour [8].
• The critical influence of temperature upon trifluorothymidine resistance in mouse lymphoma L5178Y/TK 3.7.2C cells [9].
• 18-h urine samples collected from male CD-1 mice which had been treated with either 2-aminofluorene, cyclophosphamide, or lucanthone were incubated with beta-glucuronidase, then added directly to cultures of L5178Y TK+/- mouse lymphoma cells for 3 h [10].

Biological context of Tkt

• Using fluorescent in situ hybridization analysis, the transketolase gene was mapped to mouse chromosome 16B1 and to human chromosome 3p21 [11].
• 2. Transketolase gene amplification was associated with telomeric fusion of the chromosome 16 pair together with the appearance of multiple copies of the transketolase gene throughout a different chromosome [11].
• A recombinat plasmid, pFG5, has been analyzed extensively and a detailed restriction map is presented. pFG5 DNA efficiently transforms TK- mouse L cells [4].
• RNA ribose fractional synthesis through the TK reaction using metabolites directly from glycolysis declined by 9.1 and 23.9% after OT or the combined treatment, respectively [12].
• The nucleotide sequence of independent cDNA clones revealed that TK transcripts can undergo alternative splicing within the 3' nontranslated portion of the message [13].

Anatomical context of Tkt

• The relationship between overexpression of transketolase and desensitization resistance was evaluated in somatic cell hybrids formed between a desensitization-resistant adrenal cell line and a desensitization-sensitive rat glial cell line [11].
• Interestingly, in MBP-TK mice treated for 1-20 days with FIAU, despite the ablation of more than 95% of oligodendrocytes, the protein levels of all tested nodal markers was unaltered [7].
• Second, the pattern of TK enzyme expression during differentiation was analyzed in muscle cells transformed with recombinant TK genes lacking the 3' nontranslated intron [13].
• They also provide evidence for a potential role of TK and PTP in pancreatic B-cell function [14].
• RESULTS: SDS-PAGE (-DTT) resolved mouse serum albumin and transketolase and indicated that serum albumin was 13% of the water-soluble protein in whole mouse corneas [15].

Associations of Tkt with chemical compounds

• RESULTS: Diabetic muscles showed reduced transketolase activity, which was corrected by benfotiamine [16].
• The oxidative agent menadione stimulated, while the transketolase inhibitor oxythiamine inhibited, the metabolism of dehydroascorbate in each of these three cell types [17].
• However, thiamine pyrophosphate remained tightly bound to transketolase in homogenates in which it dissociated completely from another thiamine pyrophosphate-dependent enzyme, the pyruvate dehydrogenase complex [18].
• These data suggest that loss of transketolase activity is likely to be a later consequence of thiamine deficiency in mammalian brain than is decreased activity of pyruvate dehydrogenase complex [18].
• METHODS: Serum albumin from cornea was separated from transketolase by SDS-PAGE (+/-dithiothreitol [DTT]) and identified by peptide sequencing and immunoblot analyses [15].

Other interactions of Tkt

• Islet protein, DNA and insulin contents were increased while glyceraldehyde-3-phosphate dehydrogenase and transketolase activities were reduced in female offspring [19].
• The sequences of the other cDNA fragments were identical to those of contrapsin, transketolase, and vanin-3 [20].
• The pattern of a "nonprotective" profile was composed of enolase (Eno1p), transketolase, heat shock protein and methionine synthase [21].

Analytical, diagnostic and therapeutic context of Tkt

• We show here by gene targeting that TKT-null mouse embryos are not viable and that disruption of one TKT allele can cause growth retardation ( approximately 35%) and preferential reduction of adipose tissue ( approximately 77%) [1].
• Sequence analysis supports the suggestion that present-day TKT and TKT-like genes arose from the duplication of a single common ancestral gene [22].
• In addition, Southern blot hybridization has been used to demonstrate in vivo complementation of this mutant by wt virus in both peripheral and central nervous system tissues of mice during acute infection and to show that such complementation can result in the establishment and reactivation of latent TK- infection [23].
• Thus, the overall data presented here demonstrate that TK gene therapy in combination with GM-CSF and IL-2 gene-mediated immunotherapy strategies have important implications in the treatment of breast cancer [24].

References