Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dimethyl sulfoxide (DMSO) is reported to induce hepatocyte redifferentiation. The impact of DMSO on liver transcription factors, cytochromes P450 (CYPs), and nuclear receptors regulating CYP expression was assayed in primary rat hepatocytes by QPCR. CYP 2B1, 3A1, and 4A1 mRNAs were reduced to 10-30% of initial liver levels without DMSO and restored at or above liver levels by DMSO treatment. In contrast, CYP1A1 mRNA increased approximately 5-fold during the course of culture, independent of DMSO. DMSO enhanced expression of the nuclear receptors CAR, PXR, and PPARalpha 2- to 5-fold, which may contribute to the increase in basal CYP expression. Without DMSO, liver transcription factors were decreased (HNF4, C/EBPalpha), largely unchanged (HNF1alpha, HNF3alpha, and C/EBPbeta) or elevated (HNF3beta, HNF6) compared to intact liver. DMSO largely restored hepatic levels of HNF4 and C/EBPalpha, partially suppressed the elevated levels of HNF6, increased HNF1alpha approximately 2-fold, and had little effect on HNF3alpha, HNF3beta, and C/EBPbeta. Overall, DMSO helped maintain normal hepatic transcription factor patterns and basal CYP and nuclear receptor profiles, suggesting that hepatocytes cultured with DMSO may be useful for CYP metabolic studies under conditions where the endogenous liver phenotype is preserved.
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PMID:Impact of dimethyl sulfoxide on expression of nuclear receptors and drug-inducible cytochromes P450 in primary rat hepatocytes. 1504 95

Using cytokeratin-7-positive trophoblast cells (hTr) isolated from human term placentas and the choriocarcinoma cell lines (hCC) BeWo, Jeg-3 and JAr, the expression of genes involved in the hepatobiliary excretion of cholephilic compounds was investigated by RT-PCR/sequencing followed by measurement of the absolute abundance of mRNA by real-time RT-PCR. Although mRNA of BSEP was detectable and its expression confirmed by Western blotting, its very low expression (higher in hTr than in whole placenta and hCC) did not permit its detection by immunohistochemistry. In hTr, the expression was high for OATP-B/2B1, OATP-8/1B3, MRP1, MRP3, BCRP, FIC1, RARalpha, FXR and SHP, low for OSTalpha, MRP2, MRP4, MRP8, MDR1, CAR and SXR, very low for OATP-A/1A2 and MDR3, and not detectable for OATP-C/1B1, HNF1alpha and HNF4. Expression patterns in hCC mimicked those in hTr, although some important cell line-specific differences were found. The functionality of transporters expressed in hCC was confirmed by their ability to take up and export estradiol 17beta-d-glucuronide in a self-inhibitable and temperature-sensitive manner. In conclusion, several transporters, export pumps, and nuclear receptors involved in the liver excretory function may play a similar role in the placenta, whose specific aspects can be studied by selectively using BeWo, Jeg-3 or JAr cells.
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PMID:Expression in human trophoblast and choriocarcinoma cell lines, BeWo, Jeg-3 and JAr of genes involved in the hepatobiliary-like excretory function of the placenta. 1671 28

There is increasing evidence that the magnitude and potential of intestinal nutrient absorption (sugars, fatty acids, cholesterol and triglycerides) and intestinal defense function are regulated by metabolic learning phenomena, and are influenced by dietary energy content and exercise. Metabolic overload syndromes, mainly obesity, and chronic malabsorption disorders such as inflammatory bowel disease and celiac disease have been defined as extreme phenotypes. Metabolic learning processes depend on developmental and transcriptional control systems of intestinal epithelial cell differentiation. The physiological differentiation zone of enterocytes is linked to the beta-catenin system, apolipoprotein apoA-IV and the master transcription factors Cdx2, HNF1alpha, and GATA4. In addition to these developmental regulatory transcription factors, nuclear receptors including RXR, LXR, PPAR, PXR, and CAR have been implicated in the generation of more absorptive enterocytes with a more differentiated phenotype on the one hand, and dedifferentiated cells with reduced capacity of detoxification and defense causing loss of junction control and barrier defects on the other. Large-scale analysis of gene expression profiles and identification of key pathways and master regulatory transcription factors will help dissect the role of nutritional and environmental factors as well as pharmacological intervention on mucosal homeostasis and disease, with potential applications for diagnosis and therapy.
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PMID:Metabolic learning in the intestine: adaptation to nutrition and luminal factors. 1693 81