Disease relevance of NUF2

• Although data must be gleaned from international studies representing a broad range of dosage, duration of therapy, and details reported, sufficient evidence exists to state that UDCA is approximately as effective as CDCA in dissolving gallstones [1].
• Apoptosis-inducing activity of synthetic CDCA derivatives, HS-1199 and HS-1200, on gastric cancer cell line SNU-1 cells was explored [2].
• A statistically significant increase in both CA and CDCA was observed in CP with cholestasis vis-a-vis C [3].
• This method was successfully used for the quantification of CDCA, LCA, and HDCA glucuronides formed by human liver or hepatoma HepG2 cells [4].

High impact information on NUF2

• The phospholipid to cholesterol ratio was higher during secretion of CA and UDCA as compared with DCA and CDCA [5].
• Significant inhibition of lymphocyte transformation was observed with 250 mumol/liter of either chenodeoxycholic (CDCA) or cholic acid (CA); the former caused more pronounced inhibition at higher concentrations [6].
• In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%-64%) than with taurine (36%-48%) [7].
• At a respective concentration of 1 and 100 micromol/L, LCA and CDCA induced mitochondrial damage in human fibroblasts, after just 1 hour of exposure [8].
• None of the bile acids tested, with the exception of 700 micromol/L CDCA, caused a significant release of cytosolic lactate dehydrogenase into the medium [8].

Chemical compound and disease context of NUF2

• The only other proven agent for dissolving gallstones is the 7 beta-epimer of CDCA, ursodeoxycholic acid (UDCA) [9].
• The same quantities were estimated in 16 additional patients with gallstones given chenodeoxycholic (CDCA) or ursodeoxycholic acid (UDCA) at a dose of 15 mg/kg per day in order to investigate the comparative effect of a short term (7 days) administration of the two bile acids on the hepatic sterol metabolism [10].
• Currently, the bile acids chenodeoxycholic (CDCA) and ursodeoxycholic acid (UDCA) are being used for dissolution of cholesterol gallstones in surgical high-risk patients [11].
• It was found that doubly increased MCB accounted for 1/3 of the total pigment in lithogenic guinea pig and CDCA plus glycine possessed certain protective effect from gallstone development; MCB was found in human gallstones both in bilirubinate and cholesterol type, and an unknown pigment, possibly an isomer of MCB, was found in black stone [12].

Biological context of NUF2

• In addition, a dual isotope technique for measuring the steady-state kinetics of CDCA was developed using [11,12-2H]CDCA, [24-13C]CDCA, and a single sample of serum [13].
• Analysis of the amino acid sequence of CDCA shows that the putative Cd binding site resembles that of beta-class carbonic anhydrases (CAs) [14].
• Using degenerate primers designed from the published sequences from T. weissflogii and a putative sequence in the genome of Thalassiosira pseudonana, we show that CDCA is widespread in diatom species and ubiquitous in the environment [14].
• In ileal cells CDCA, through the FXR, up-regulates the expression of the ileal bile acid-binding protein (IBABP), implicated in the enterohepatic circulation of bile acids [15].
• CDCA derivatives demonstrated various apoptosis hallmarks, such as mitochondrial changes, activation of caspase, DNA fragmentation, and nuclear condensation [2].

Anatomical context of NUF2

• The unconjugated and conjugated forms of cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA) and lithocholic acid (LCA) were added to calf thymus DNA followed by 1 h of incubation at 37 degrees C. After the incubation the mixture was analyzed by the nuclease P1 modification of 32P-postlabeling [16].
• We report that UDCA (100 and 200 microM) induced a moderate increase of IBABP mRNA (approximately 10% of the effect elicited by 50 microM CDCA) in enterocyte-like Caco-2 cells and approximately halved the potent effect of CDCA (50 microM) [15].
• Gallbladder bile was unsaturated in all CDCA- and UDCA-treated patients [17].
• Importantly, the orphan receptor Nur77 (TR3) was shown to translocate from the nucleus to mitochondria at the early time points after CDCA derivatives treatment [2].
• No significant alterations in epithelial cell proliferation were observed among patients treated with UDCA or CDCA with the exception of the number of cells per crypt column which, in the latter instance, deviated only slightly from the predicted values [11].

Associations of NUF2 with chemical compounds

• In summary, these data demonstrate that the steady-state kinetics of CDCA and CA and the pool size of DCA can be measured from the serum of healthy subjects [13].
• The data on the extent of binding at a concentration of 0.1 mg/ml showed values of 28.5 (t-LCA), 23.7 (g-LCA), 3.47 (LCA) and 1.32 (CDCA) adducts per 10(8) nucleotides [16].
• The calcium binding affinities followed the pattern: dihydroxy (CDCA, UDCA and DCA) greater than trihydroxy (CA and UCA) bile acids, and glycine conjugates greater than taurine conjugates [18].
• Chenodeoxycholic acid (chenic acid; CDCA) is 1 of the 3 major biliary bile acids in man [9].
• Lineshape analysis of spectra of the protonated form of nor-CDCA at acidic bulk pH indicated that the transbilayer transport rate of nor-CDCA (580 sec-1) was six times faster than that of CDCA (100 sec-1) [19].

Other interactions of NUF2

• A recent report of a novel carbonic anhydrase (CDCA1) with Cd as its metal centre in the coastal diatom Thalassiosira weissflogii has led us to search for the occurrence of this Cd enzyme (CDCA) in other marine phytoplankton and in the environment [14].

Analytical, diagnostic and therapeutic context of NUF2

• Using real-time quantitative PCR and cotransfection reporter assays, we demonstrate that the RXR agonist LG100268 antagonizes induction of BSEP expression mediated by endogenous and synthetic FXR ligands, CDCA and GW4064, respectively [20].
• In the control group, cholic acid (CA) was the predominant bile acid and comprised 76% of TBA and chenodeoxycholic (CDCA) accounted for about 13% of the total [21].
• Free and conjugated ursodeoxycholic (UDCA), cholic (CA), lithocholic (LCA), deoxycholic (DCA) and chenodeoxycholic (CDCA) acids were evaluated by CE (capillary electrophoresis) in 41 patients (15 of them simultaneously by HPLC), in 30 healthy pregnant women and in 10 non-pregnant women [22].
• Serum primary bile acid (cholic (CA) and chenodeoxycholic (CDCA) acid) concentrations were measured in 14 preterm and 11 full-term hyperbilirubinaemic newborns at the beginning and end of, and 24 and 72 hours following phototherapy [23].
• Tupaias (tree shrews) -- a new animal model for gallstone research. III. Cholesterol metabolism under different diets and CDCA [24].

References