Disease relevance of Chenodeoxycholylglycine

• Although bile acids do not activate NF-kappaB, NF-kappaB activation by cytokines (induced during cholestasis) protected against GCDCA-induced apoptosis in vitroby upregulating A1 and cIAP2 [1].
• A significantly large proportion of 3-sulfated glycochenodeoxycholic acid, i.e., 21.9 to 31.3% of total glycochenodeoxycholic acid, was found in the serum of patients with obstructive jaundice [2].
• METHODS: The Barrett's adenocarcinoma cell line, SEG-1, was exposed to the conjugated bile salt, glycochenodeoxycholic acid (GCDA) [3].
• Our data show that GCDCA (75 microM, 4 h) significantly upregulates cFos and JunB as demonstrated by microarray analysis and real-time PCR in HepG2-Ntcp hepatoma cells [4].

High impact information on Chenodeoxycholylglycine

• The surface phosphate content was diminish by increasing glycochenodeoxycholic acid concentrations, and this relationship was interpreted as competition between bile acid and HPO4(-4) for binding sites on the calcium phosphate surface [5].
• Similar results were obtained with cholylsarcosine (a deconjugation-dehydroxylation resistant analogue) or with chenodeoxycholylglycine, the endogenous bile acid of the guinea pig [6].
• GCDCA induces apoptosis in a mitochondria-controlled pathway in which caspase-8 is activated in a Fas-associated protein with death domain-independent manner [1].
• Hepatocytes were exposed to GCDCA, TUDCA, the glyco-conjugate of UDCA (GUDCA), and TCDCA [7].
• These observations suggest the existence of an intestinal control mechanism in healthy man, whereby presence of glycochenodeoxycholic acid in the ileum inhibits motility and delays transit in the jejunum and ileum [8].

Biological context of Chenodeoxycholylglycine

• Our results demonstrated that uptake of GCDCA is needed for apoptosis induction [7].
• In contrast to cytolysis, apoptosis with DNA fragmentation was induced by low concentrations of glycochenodeoxycholic acid a few hours after incubation [9].
• NES cells exposed to 5 min of GCDA did not increase cell number [10].
• Glycochenodeoxycholic acid treatment up-regulated phosphorylation of stress-activated protein kinase/c-jun-NH2-terminal kinase which was inhibited by honokiol treatment [11].
• Honokiol reduces oxidative stress, c-jun-NH2-terminal kinase phosphorylation and protects against glycochenodeoxycholic acid-induced apoptosis in primary cultured rat hepatocytes [11].

Anatomical context of Chenodeoxycholylglycine

• Effect of ileal infusion of glycochenodeoxycholic acid on segmental transit, motility, and flow in the human jejunum and ileum [8].
• Using a radiometric assay with glycochenodeoxycholic acid as substrate, bile acid:3'-phosphoadenosine-5'-phosphosulfate sulfotransferase activity was found in 105,000 g supernatant fractions of liver, proximal intestine, and adrenal gland homogenates from adult hamsters [12].
• The MMPT was measured spectrophotometrically and morphologically in rat liver mitochondria exposed to glycochenodeoxycholic acid (GCDC) [13].
• In conclusion, in a non-neoplastic Barrett's cell line, GCDA exposure induces proliferation by activation of both ERK and p38 MAPK pathways [10].
• The increase in biliary GLCA probably resulted from bacterial biotransformation of glycochenodeoxycholic acid to lithocholic acid and its increased absorption from the cecum during TPN [14].

Associations of Chenodeoxycholylglycine with other chemical compounds

• RESULTS: Glycochenodeoxycholic acid (GCDCA 75 micromol/l) induced apoptosis was reduced by sulfasalazine dose dependently (1-1000 micromol/l) in HepG2-Ntcp cells whereas its metabolites 5-ASA and sulfapyridine had no effect [15].
• In contrast to TCDCA and TUDCA, GCDCA induced apoptosis in a Fas-associated protein with death domain (FADD)-independent pathway in hepatocytes [16].
• At the higher dose, ketoconazole produced a significant increase in serum levels of cholic acid, taurocholic acid, chenodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid and taurochenodeoxycholic acid compared with the control group (P < .05) [17].
• In freshly isolated rat hepatocyte suspensions that were exposed to the toxic hydrophobic bile acid glycochenodeoxycholic acid (100 or 500 microM), betaC (100 microM) decreased generation of reactive oxygen species by >50%, similar to the inhibition afforded by alpha-tocopherol [18].
• Chenodeoxycholyltaurine and chenodeoxycholylglycine were the GSH cosubstrates with the highest affinities for ABCC4, with K(m) values of 3.6 and 5.9 microM, respectively [19].

Gene context of Chenodeoxycholylglycine

• GCDA-induced MAPK activation was examined by Western blot analysis for phosphorylated ERK and p38 [10].
• In BAR cells, GCDA exposure increased cell number by 31%, increased phosphorylated p38 and ERK levels by two- to three-fold, increased BrdU incorporation by 30%, and decreased UV-induced apoptosis by 15-20% [10].
• Thus, GCDCA-induced upregulation of AP-1-dependent genes appears important for the cytotoxicity of this bile acid [4].
• Apoptosis was measured by TdT-mediated dUTP nick-end labeling and annexin V staining after GCDA and UV-B exposure [10].
• Chenodeoxycholylglycine was elevated in most sera of patients who had hepatitis, cholestasis, or hepatic malignancy [20].

Analytical, diagnostic and therapeutic context of Chenodeoxycholylglycine

• (4) The combination of [14C]aminopyrine breath test and postprandial levels of GCDCA enhance the diagnostic value, specificity, and sensitivity in the assessment of patients with CLD [21].
• Perfusion studies of the terminal ileum were performed in healthy volunteers to define the influence of a dihydroxy bile acid, glycochenodeoxycholic acid (GCDC) 2.5 mmol/l, on the mechanisms of electrolyte transport [22].
• Pregnancy serum glycochenodeoxycholic acid (GCDA) and taurochenodeoxycholic acid (TCDA) were simultaneously assayed by solid-phase fluoroimmunoassay (FIA) for apparently healthy Nigerians and caucasians domiciled in Nigeria and London respectively [23].

References