Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the last few years, increasing evidence has become available that some chemicals may have thyroid hormone- disrupting potencies. The effects exerted via thyroid hormone receptors (TR) have not been studied thoroughly. The present study investigates chemical thyroid hormone disruption at the level of TR functioning. To this end the (ant)agonistic action of a series of xenobiotics was tested in the newly developed yeast two-hybrid assay. This assay makes use of recombined TRbeta gene and reporter gene yeast, which specifically expresses beta-galactosidase when incubated with exogenous 3,3',5-triiodo-l-thyronine (T(3)). Agonistic and antagonistic actions were studied in the absence and presence of 5 x 10(-6) mol/L T(3), which induced maximal beta-galactosidase activity. The compounds tested included the specific TR-antagonist amiodarone, as well as a series of phenols, phthalate, organochlorine pesticides (OCPs), polyhalogenated aromatic hydrocarbons (PHAHs) with structural similarity to T(3), and 3,3',5,5'-tetraiodo-l-thyronine (T(4)). The results obtained reveal that only 2-t-butylphenol and 2-isopropylphenol are specific agonists. Interestingly, some compounds showed potentiated antagonistic effects when tested in combination with T(3), which suggests that TR-mediated transcription may be disrupted in vivo. The 20% relative inhibitory concentration (RIC20) values of phenols, ester and OCPs were more than 10(-7) mol/L, but the values for PHAHs with metabolization were lower than 5 x 10(-7) g/L. These results suggest that PHAHs pose a serious threat to the human thyroid system. Altogether the results of the present study show that the newly developed, yeast two-hybrid assay can be used as a valuable tool for identification and quantification of compounds active in disturbing thyroid hormone homeostasis at the level of TR. The results are further evidence of thyroid-related effects of environmentally relevant PHAHs.
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PMID:A two-hybrid yeast assay to quantify the effects of xenobiotics on thyroid hormone-mediated gene expression. 1809 57

The aim of this study is to investigate the chemical retinoic acid (RA) disruption at the level of retinoid X receptor (RXR) functioning. This assay makes use of recombined human RXR gene and reporter gene yeast, which specifically expresses beta-galactosidase when incubated with exogenous 9-cis retinoic acid (9-cis RA). Agonistic and antagonistic actions of chemicals including a series of phenols, phthalates, organochlorine pesticides (OCPs) were tested in the absence and presence of 5 x 10(-6)mol/L 9-cis RA, at which maximal beta-galactosidase activity could be induced. The results obtained reveal that some chemicals, e.g., 2-t-butylphenol, 2-isopropylphenol, 2,4-dichlorophenol (2,4-DCP), 3,4-dichlorophenol (3,4-DCP), 4-tert-octylphenol (4-t-OP) and hexachlorobenzene (HCB), are RXR agonists. Especially, bisphenol A (BPA) showed high induction activity to RXR when tested with metabolization. The 20% relative inhibitory concentration (RIC20) values of r-hexachlorocyclohexane (HCH), p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and 2,4-DCP with metabolization were lower than 1 x 10(-6)mol/L. These results suggest that BPA, HCH, p,p'-DDT and 2,4-DCP are chemicals that pose a threat to hRXR functioning. Altogether the results of the present study show that the newly developed, yeast two-hybrid assay can be used as a valuable tool for identification and quantification of compounds active in disturbing retinoid homeostasis at the level of RXR.
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PMID:A two-hybrid yeast assay to quantify the effects of xenobiotics on retinoid X receptor-mediated gene expression. 1820 73