Disease relevance of Tpi1

• Although activity alteration was also found in liver, lung, kidney, spleen, heart, brain and muscle the TPI deficiency in heterozygotes has no influence on the following physiological traits: hematological parameters, plasma glucose, glucose consumption of blood cells, body weight and organo-somatic indices of liver, spleen, heart, kidney and lung [1].
• The molecular probes are derived from the mouse mammary tumor virus envelope gene, the ornithine decarboxylase gene, and the triose phosphate isomerase gene [2].
• Of 15 isozymes located on different mouse chromosomes only triosephosphate isomerase segregated syntenic with the M-MuLV gene, suggesting that the virus was integrated on chromosome No. 6. This was confirmed by sexual genetic experiments analyzing segregation of Moloney viremia and two markers on chromosome 6 and 15, respectively [3].
• Our microarray experiments revealed a number of CB-expressed genes (e.g. TH, ferritin and triosephosphate isomerase) that were known to change their expression under hypoxia [4].
• Continuous alveolar macrophage (AM) and tumor-infiltrated (TIM) cell lines have been generated from C57B16J mice by in vitro infection with the J2 retrovirus carrying the v-raf and v-myc oncogens [5].

High impact information on Tpi1

• CD22 signaling is mediated via interactions with a number of kinases and phosphatases that bind the cytoplasmic domain through phosphorylated tyrosine residues located within consensus TAM and TIM motifs [6].
• (i) A suppressor tRNA, which acts in trans to suppress an amber nonsense codon within TPI mRNA, and (ii) a hairpin structure in the 5' untranslated region of TPI mRNA, which acts exclusively in cis to inhibit initiation of TPI mRNA translation, were found, individually, and to a greater extent, together, to abrogate the decrease in mRNA [7].
• Evidence to implicate translation by ribosomes in the mechanism by which nonsense codons reduce the nuclear level of human triosephosphate isomerase mRNA [7].
• The abundance of the mRNA for human triosephosphate isomerase (TPI) is decreased to 20-30% of normal by frameshift and nonsense mutations that prematurely terminate translation within the first three-quarters of the reading frame [7].
• TPI pre-mRNA harbors six introns that are constitutively removed by splicing [8].

Chemical compound and disease context of Tpi1

• RESULTS: After 7 to 14 days in co-culture with UMR106 osteoblast-like cells in the presence of 1,25-dihydroxy vitamin D3, only cells of the TIM population differentiated into osteoclast-like cells (nonspecific esterase-negative: tartrate-resistant acid phosphatase-positive) capable of extensive lacunar bone resorption [9].
• When cells expressing the recombinant TPI protein with histidine tag were exposed to hypoxia and the TPI protein was affinity-purified, the catalytic activity (specific activity) of the TPI protein purified from hypoxic cells was substantially lower than that obtained from normoxic cells [10].
• The induction of TPI gene expression by hypoxia was suppressed by (1) a chelator of intracellular Ca(2+), (2) a blocker of non-selective cation channels, (3) a blocker of Na(+)/Ca(2+) exchangers, (4) an inhibitor of Ca(2+)/calmodulin-dependent protein kinases, and (5) an inhibitor of c-jun/AP-1 activation [10].

Biological context of Tpi1

• It is shown that Tpi-1 and Gapd are closely linked on chromosome 6, with a recombination frequency of 0.1 +/- 0.1% [11].
• Biochemical investigations of TPI in both mutant genotypes revealed neither physicochemical nor kinetic differences compared to the wild type [12].
• Nucleotide sequence of murine triosephosphate isomerase cDNA [13].
• Because of this phenotype and a close linkage to the Tpi gene, the Mitf gene was considered as a candidate gene [14].
• All mutations were found to be homozygous lethal at an early postimplantation stage of embryonic development, probably due to a total lack of TPI activity and consequently to the inability to utilize glucose as a source of metabolic energy [1].

Anatomical context of Tpi1

• Assignment of a Mus musculus gene for triosephosphate isomerase to chromosome 6 and for glyoxalase-I to chromosome 17 using somatic cell hybrids [15].
• The dependence of TPI RNA 3'-end formation on splicing may reflect the suboptimal strengths of the corresponding regulatory sequences and may function to ensure that TPI pre-mRNA is not released from the chromatin template until it has formed a complex with spliceosomes [8].
• In cultured cells, little if any mRNA accumulates from an intronless version of the human gene for triosephosphate isomerase (TPI), a gene that normally contains six introns [16].
• Tim-3, a member of the T cell Ig mucin (TIM) family regulates effector Th1 responses [17].
• These Ag as well as two 28 kDa proteins, triosephosphate isomerase and glutathione S-transferase, in purified native or recombinant form or as a synthetic peptide, stimulated lymphocyte proliferation [18].

Associations of Tpi1 with chemical compounds

• A mutation resulting in increased triosephosphate isomerase (TPI) activity in blood was recovered in offspring of procarbazine hydrochloride-treated male mice [12].
• Four heterozygous triosephosphate isomerase (TPI) mutants with approximately 50% reduced activity in blood compared to wild type were detected in offspring of 1-ethyl-1-nitrosourea treated male mice [1].
• However, the step in TPI RNA metabolism that is altered was not defined, and the use of actinomycin D, in affecting all polymerase II-transcribed genes, could result in artifactual conclusions [19].
• This study substantiates that the five Ag, paramyosin, heat shock protein 70, triosephosphate isomerase, glutathione S-transferase, and the integral membrane protein Sm23, are important candidates for a defined antischistosomal vaccine [18].
• Oxidation of purified enolase or TPI via Fenton chemistry led to a 17 or 23% loss of activity, respectively, confirming that a loss of activity was the consequence of oxidation [20].

Other interactions of Tpi1

• Tpi-1 and Gapd are linked very closely on mouse chromosome 6 [11].
• The study furthermore suggests one functional TPI gene per haploid genome in the erythrocyte and seven other tested organs of the mouse [1].
• The crystal structure of Ym1 consists of two globular domains, a beta/alpha triose-phosphate isomerase barrel domain and a small alpha + beta folding domain [21].
• Old mice on CR showed significant decreases in the activities of all the enzymes studied, except for aldolase, triosephosphate isomerase and phosphoglycerate mutase, which were unchanged [22].
• The activities of some glycolytic enzymes, phosphoglycerate kinase, glyceraldehyde-phosphate dehydrogenase, phosphoglyceromutase and triosephosphate isomerase are reduced (P less than 0.05) [23].

Analytical, diagnostic and therapeutic context of Tpi1

• To examine the consequences of GAPDH inhibition upon neuronal survival, we exposed murine neocortical cell cultures to the inhibitor of GAPDH and triosephosphate isomerase, alpha-monochlorohydrin [24].
• Exons of the TPI gene from control mice and heterozygous mutant mice were PCR amplified and sequenced as necessary to determine the molecular lesion in the mutant alleles [25].
• Only one mab out of fifteen cross-reacted in direct ELISA binding to all amylases and triose phosphate isomerase [26].

References