Enhanced modulation

Sugatani J, Kojima H, Ueda A et al (2001) The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Hepatology 33 1232-1238... 

X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene. Molecular and Cellular Biology, 18,... 

Kitagawa C, Ando M, Ando Y et al. Genetic polymorphism in the phenobarbital-responsive enhancer module of the UDP-glucuronosyltransferase lAl gene and irinotecan toxicity. Pharmacogenet Genomics 2005 15 35 1. 

Figure 5.34 Mechanism of induction of CYP2B6 by a chemical such as the drug phenobarbital. This drug activates a nuclear receptor (CAR).This combines with the retinoid X receptor and binds to PBREM, as specific section of the CYP gene, which stimulates the production of CYP2B6 mRNA leading to the production of CYP2B6 protein and enzyme. Abbreviations CAR, constitutive androstane receptor RXR retinoid X receptor PBREM, phenobarbital-responsive enhancer module.

Graaff, A.M., et al. 2003. Combined chemical and electrical enhancement modulates stratum corneum structure. J Control Release 90 49. 

Figure 9.10 Illustration depicting DNA elements found in CYP3A genes and the activation of the human pregnane X receptor (PXR) by ligand (RIF) and subsequent transcriptional activation of CYP3A4 gene by the PXR/RXR heterodimer. dNR-1-3, nuclear receptors 1, 2, and 3, respectively PXR, pregnane X receptor RXR, retinoid X receptor RIF, rifampicin SRC-1, steroid receptor co-activator XREM, xenobiotic responsive enhancer module.

Matsumura et al. (147) identified a novel enhancer module, CLEM4, far upstream (about 11 kb) in the human CYP3A4 gene. CLEM4 binds multiple transcription factors, some of them liver-specific such as HNF-4. 

CLEM4 appears to regulate constitutive expression of CYP3A4 rather than induction this is reflected in its acronym, which stands for constitutive liver enhancer module. CLEM4 is polymorphic in Caucasians a TGT insertion disrupts a USF1 binding site and reduces enhancer activity about 35% in a reporter gene system in vitro. The TGT insertion allele is present at a frequency of about 3% in Caucasian subjects but was not found in I3l Japanese subjects (147). 

Park EY, Cho IJ, Kim SG. Transactivation of the PPAR-responsive enhancer module in chemopreventive glutathione S-transferase gene by the peroxisome proliferator-activated receptor-gamma and retinoid X receptor heterodimer. Cancer Res 2004 64 3701-3713. 

Makinen J, Frank C, Jyrkkarinne J, Gynther J, Carlberg C, Flonkakoski P. Modulation of mouse and human phenobarbital-responsive enhancer module by nuclear receptors. Mol Pharmacol 2002 62 366-378. 

Sugatani J, Yamakawa K, Tonda E, Nishitani S, Yoshinari K, Degawa M, Abe I, Noguchi H, Miwa M. The induction of human UDP-glucuronosyl-transferase 1A1 mediated through a distal enhancer module by flavonoids and xenobiotics. Biochem Pharmacol 2004 67 989-1000. 

Goodwin B, Hodgson E, Liddle C. The orphan human pregnane X receptor mediates the transcription activation of CYP3A4 by rifampicin through a distal enhancer module. Mol Pharmacol 1999 56 1329-39. 

Frenander U and Jdnsson AS, Cell harvesting by crossflow microfiltration using a shear-enhanced module, Biotechnol. Bioeng. 1996 52 397. 

Because high fluxes and the abdity to process streams containing suspended solids and fibers are often wanted in the pulp and paper industry, high-shear modules have been developed. Currently existing high-shear modules, excluding tubular modules, are modified plate and frame constructions. Both a cross-rotational module from Metso Paper and a vibration enhanced module (VSEP) from New Logic Inc. have been industrially used or tested in pulp and paper industry applications [48-51]. 

Honkakoski P, Moore R, Washburn KA, et al. Activation by diverse xenochemi-cals of the 51-base pair phenobarbital-responsive enhancer module in the CYP2B10 gene. Mol Pharmacol 1998 53 597-601. 

Honkakoski P, Negishi M. Characterization of a phenobarbital-responsive enhancer module in mouse P450 Cyp2bl0 gene. J Biol Chem 1997 272 14943 19. 

B. Distinct Enhancer Modules of mef2 Linking Patterning and Differentiation Events... 

Honkakoski, P., Zelko, I., Sueyoshi, T. and Negishi, M. (1998) The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene. Molecular and Cellular Biology, 18, 5652-5658. 

Modern-day, air-filtering, military respirators consist of a facepiece (mask), on which are mounted various sub-assembly components such as filters, faceseals, visors/eyepieces, valves, air-guides, speech-enhancing modules and drinking systems. 

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