Disease relevance of L-gularic acid

• Localization of mucin (MUC2 and MUC3) messenger RNA and peptide expression in human normal intestine and colon cancer [1].
• BACKGROUND & AIMS: Expression of mucin MUC2, the structural component of the colonic mucus layer, is lowered in inflammatory bowel disease [2].
• Effects of diet on glucaric acid concentration in bile and the formation of calcium bilirubinate gallstones [3].
• Altered expression and allelic association of the hypervariable membrane mucin MUC1 in Helicobacter pylori gastritis [4].
• Very early noninvasive detection of acute experimental nonreperfused myocardial infarction with 99mTc-labeled glucarate [5].

Psychiatry related information on L-gularic acid

• 4. Moderate alcohol consumption in 18 healthy volunteers did not significantly augment the urinary D-glucaric acid excretion [6].

High impact information on L-gularic acid

• All receptor-independent retinoids and two receptor-dependent retinoids induced apoptosis, and the induction correlated significantly with increased expression of the mucin MUC1 (r =.83; P =.03) [7].
• Retinoids with ester-linking groups did not induce apoptosis but decreased the growth fraction in correlation with MUC1 induction (r = -.93; P =.02) [7].
• Evidence that gallbladder epithelial mucin enhances cholesterol cholelithogenesis in MUC1 transgenic mice [8].
• In the present study, bile levels of glucaro-1:4-lactone (measured as glucaric acid) the leading inhibitor of beta-glucuronidase, were measured in both man and in rats fed high, medium, and low protein-fat diets [3].
• For our studies, we have selected an epitope from the tandem-repeat unit of the high-molecular-weight MUC2 mucin glycoprotein, which can be underglycosylated in case of colon cancer [9].

Chemical compound and disease context of L-gularic acid

• Metabolism of glucurolactone to glucarate in Parkinson's disease [10].
• Crystals of GlucD have been obtained into which the substrate D-glucarate and two competitive inhibitors, 4-deoxy-D-glucarate and xylarohydroxamate, could be diffused; D-glucarate is converted to the dehydration product, 5-keto-4-deoxy-D-glucarate (KDG) [11].
• The membrane epithelial mucin MUC1 is expressed at the luminal surface of most simple epithelial cells, but expression is greatly increased at lactation and in most breast carcinomas [12].
• Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism [13].
• Incubation of the solid-phase HS substrates with B16 melanoma cell extracts in the presence of D-saccharic acid 1,4-lactone (a potent exo-beta-glucuronidase inhibitor) resulted in the time- and dose-dependent release of [14C]HS fragments [14].

Biological context of L-gularic acid

• Association of ulcerative colitis with rare VNTR alleles of the human intestinal mucin gene, MUC3 [15].
• GSK3beta-mediated phosphorylation of MUC1 had no apparent effect on beta-catenin levels or the transcriptional coactivation function of beta-catenin [16].
• FLVCR has significant amino acid sequence homology with members of the major facilitator superfamily and especially D-glucarate transporters described in bacteria and in C. elegans [17].
• Last, variably penetrant maternal blood sinus dilation in Muc1-deficient placentas suggests that Muc1 regulation by PPARgamma contributes to normal placental development but also that the essential functions of PPARgamma in the organ are mediated by other targets [18].
• The results, however, demonstrate that MUC1 expression decreases binding of beta-catenin to the E-cadherin cell adhesion molecule [16].

Anatomical context of L-gularic acid

• Another group of rabbits (n = 6) with 5 or 15 minutes of LAD occlusion were used to assess the affinity of 99mTc glucarate for the ischemic myocardium [5].
• Recently, a highly glycosylated mucin MUC1 was detected on a majority of multiple myeloma cell lines [19].
• We analyzed bone marrow and peripheral blood of 68 patients with HLA-A2-positive myeloma for the presence and functional activity of CD8 T cells specific for the MUC1-derived peptide LLLLTVLTV [19].
• Here, we show that the mucin gene Muc1 is a PPARgamma target, whose expression is lost in PPARgamma null placentas [18].
• Forty-four percent of the patients with MM contained elevated frequencies of MUC1-specific CD8 T cells in freshly isolated samples from peripheral blood (PB) or bone marrow (BM) compared with corresponding samples from healthy donors [19].

Associations of L-gularic acid with other chemical compounds

• In contrast, various nonspecific lysosomotropic agents such as ammonium chloride and D-saccharic acid lactone led to a marked inhibition of the cytotoxic action of TNF in vitro [20].
• The beta-glucuronidase inhibitor, saccharic acid 1,4-lactone, significantly reduced the H2O2-metabolizing ability of the Scutellaria cells, indicating that beta-glucuronidase, which does not catalyze the H2O2 degradation, plays an important role in the H2O2 metabolism [21].
• The properties of the enzyme, including molecular weight, amino acid composition, electrophoretic behavior, and kinetic features, distinguish it from similar dehydrogenases induced in the same cell strain by hydroxyproline or by glucarate [22].
• Urinary D-glucaric acid excretion during rifampicin/isoniazid and anticonvulsant enzyme induction [23].
• As measured by urinary D-glucaric acid excretion, an index of hepatic enzyme induction, glutethimide was the most powerful of six such inducers tested [23].

Gene context of L-gularic acid

• Muc1 promoter is activated strongly and specifically by liganded PPARgamma but not PPARalpha or PPARdelta [18].
• Differential mucin MUC7 gene expression in invasive bladder carcinoma in contrast to uniform MUC1 and MUC2 gene expression in both normal urothelium and bladder carcinoma [24].
• These results were consistent with immunoblots using anti-MRP (MUC2 repeat peptide), anti-M3P (MUC3 repeat peptide), 139H2 (MUC1 peptide), anti-T (peanut lectin), anti-Tn (91S8), and anti-sialosyl Tn (JT10e) antibodies [25].
• Cloning and analysis of cDNA encoding a major airway glycoprotein, human tracheobronchial mucin (MUC5) [26].
• Differential expression of the human mucin genes MUC1 to MUC5 in relation to growth and differentiation of different mucus-secreting HT-29 cell subpopulations [27].

Analytical, diagnostic and therapeutic context of L-gularic acid

• After confirmation of LAD occlusion by 201Tl scintigraphy, a mixture of 99mTc glucarate (15.7 +/- 1.6 mCi) and 111In anti-myosin (0.53 +/- 0.03 mCi) was administered intravenously [5].
• The feasibility of imaging with 99mTc glucarate was evaluated for the early diagnosis of nonreperfused and reperfused myocardial infarction and compared with localization of simultaneously administered 111In anti-myosin [5].
• A decrease in MUC4 expression, confirmed by Western blot and immunofluorescence analyses, resulted in diminished growth and clonogenic ability of antisense-MUC4-transfected (EIAS19) cells compared with parental, empty vector (ZEO) and sense transfected (ES6) control cells [28].
• The noninvasive urinary parameters investigated were thioethers, D-glucaric acid, elements, and forward and reverse mutagenesis using bacterial bioassays [29].
• In preparation for clinical trials, vaccines containing synthetic MUC1 peptides of different lengths and sequences mixed with various adjuvants or covalently attached, using different linker methods, to protein carrier keyhole limpet hemocyanin (KLH) were studied in mice [30].

References