The Experts below are selected from a list of 180 Experts worldwide ranked by ideXlab platform

Ying Huang - One of the best experts on this subject based on the ideXlab platform.

  • cytochrome p450 dependent Biotransformation of Xenobiotics in human and rodent embryonic tissues
    Drug Metabolism Reviews, 1998
    Co-Authors: Mont R Juchau, Helene Bouteletbochan, Ying Huang
    Abstract:

    Profound species differences and developmental stage differences as well as a lack of solid data prevent broad, sweeping generalizations in terms of statements that can be made concerning the prenatal expression of individual P450 isoforms. It is clear, however, that several of such isoforms are expressed at levels that can be toxicologically significant. At present, the greatest interest appears to be in P450s 1A1, 1B1, 2E1, and 3A7, each of which has been reported to be expressed at toxicologically significant levels or at least at potentially toxicologically significant levels during organogenesis. Reports of the expression of other P450 isoforms at later stages of gestation also have appeared in the recent literature.

Hansruedi Gla - One of the best experts on this subject based on the ideXlab platform.

  • sulfation and sulfotransferases 4 bioactivation of mutagens via sulfation
    The FASEB Journal, 1997
    Co-Authors: Hansruedi Gla
    Abstract:

    Sulfation is a common final step in the Biotransformation of Xenobiotics and is traditionally associated with inactivation. However, the sulfate group is electron-withdrawing and may be cleaved off heterolytically in some molecules, leading to an electrophilic cation. The stable heterologous expression of sulfotransferases in indicator cells of standard mutagenicity tests has substantially improved the accessibility of this activation pathway. Sulfotransferase-mediated genotoxic effects have been demonstrated for numerous benzylic alcohols derived from polycyclic aromatic hydrocarbons and various aromatic hydroxylamines. Also, hycanthone (a benzylic alcohol), alpha-hydroxytamoxifen (an allylic alcohol), 1'-hydroxysafrole (an allylic/benzylic alcohol), and 2-nitropropane are activated to genotoxicants by sulfotransferases. Various reactive sulfate conjugates show strong mutagenic effects only when they are generated directly within the indicator cell, due to their inefficient penetration of cell membranes....

Takashi Iyanagi - One of the best experts on this subject based on the ideXlab platform.

  • molecular mechanism of phase i and phase ii drug metabolizing enzymes implications for detoxification
    International Review of Cytology-a Survey of Cell Biology, 2007
    Co-Authors: Takashi Iyanagi
    Abstract:

    Enzymes that catalyze the Biotransformation of drugs and Xenobiotics are generally referred to as drug-metabolizing enzymes (DMEs). DMEs can be classified into two main groups: oxidative or conjugative. The NADPH-cytochrome P450 reductase (P450R)/cytochrome P450 (P450) electron transfer systems are oxidative enzymes that mediate phase I reactions, whereas the UDP-glucuronosyltransferases (UGTs) are conjugative enzymes that mediate phase II enzymes. Both enzyme systems are localized to the endoplasmic reticulum (ER) where a number of drugs are sequentially metabolized. DMEs, including P450s and UGTs, generally have a highly plastic active site that can accommodate a wide variety of substrates. The P450 and UGT genes constitute a supergene family, in which UGT proteins are encoded by distinct genes and a complex gene. Both the P450 and UGT genes have evolved to diversify their functions. This chapter reviews advances in understanding the structure and function of the P450R/P450 and UGT enzyme systems. In particular, the coordinate Biotransformation of Xenobiotics by phase I and II enzymes in the ER membrane is examined.

  • functional co expression of xenobiotic metabolizing enzymes rat cytochrome p450 1a1 and udp glucuronosyltransferase 1a6 in yeast microsomes
    Biochimica et Biophysica Acta, 2004
    Co-Authors: Shinichi Ikushiro, Masahiro Sahara, Yoshikazu Emi, Yoshiyasu Yabusaki, Takashi Iyanagi
    Abstract:

    Xenobiotic Phase I and Phase II reactions in hepatocytes occur sequentially and cooperatively during the metabolism of various chemical compounds including drugs. In order to investigate the sequential metabolism of 7-ethoxycoumarin (7EC) as model substrate in vitro, xenobiotic metabolizing enzymes, rat cytochrome P450 1A1 (P450 1A1) and UDP-glucuronosyltransferase 1A6 (UGT1A6) were co-expressed in Saccharomyces cerevisiae AH22. Rat P450 1A1 and yeast NADPH-P450 reductase were expressed on a multicopy plasmid (pGYR1) in the yeast. Rat UGT1A6 cDNA with a yeast alcohol dehydrogenase I promoter and terminator was integrated into yeast chromosomal DNA to achieve the stable expression. Co-expression of P450 1A1 and UGT1A6 in yeast microsomes was confirmed by immunoblot analysis. Protease treatment of the microsomes showed the correct topological orientation of UGT to the membranes. The metabolism of 7EC to 7-hydroxycoumarin (7HC) and its glucuronide in yeast microsomes was analyzed by reverse phase HPLC. In a co-expression system containing 7EC, NADPH and UDP-glucuronic acid, glucuronide formation was detected after a lag phase, following the accumulation of 7HC. In the case of P450 1A1 and UGT1A6, efficient coupling of hydroxylation and glucuronidation in 7EC metabolism was not observed in the co-expression system. This P450 and UGT co-expression system in yeast allows the sequential Biotransformation of Xenobiotics to be simulated in vitro.

Beatrice L Poolzobel - One of the best experts on this subject based on the ideXlab platform.

  • apple flavonoids inhibit growth of ht29 human colon cancer cells and modulate expression of genes involved in the Biotransformation of Xenobiotics
    Molecular Carcinogenesis, 2006
    Co-Authors: Selvaraju Veeriah, Nina Habermann, Tanja Kautenburger, Julia Sauer, H Dietrich, Frank Will, Beatrice L Poolzobel
    Abstract:

    Flavonoids from fruits and vegetables probably reduce risks of diseases associated with oxidative stress, including cancer. Apples contain significant amounts of flavonoids with antioxidative potential. The objectives of this study were to investigate such compounds for properties associated with reduction of cancer risks. We report herein that apple flavonoids from an apple extract (AE) inhibit colon cancer cell growth and significantly modulate expression of genes related to xenobiotic metabolism. HT29 cells were treated with AE at concentrations delivering 5–50 µM of one of the major ingredients, phloridzin (“phloridzin-equivalents,” Ph.E), to the cell culture medium, with a synthetic flavonoid mixture mimicking the composition of the AE or with 5–100 µM individual flavonoids. HT29 cell growth was inhibited by the complex extract and by the mixture. HT29 cells were treated with nontoxic doses of the AE (30 µM, Ph.E) and after 24 h total RNA was isolated to elucidate patterns of gene expression using a human cDNA-microarray (SuperArray®) spotted with 96 genes of drug metabolism. Treatment with AE resulted in an upregulation of several genes (GSTP1, GSSTT2, MGST2, CYCP4F3, CHST5, CHST6, and CHST7) and downregulation of EPHX1, in comparison to the medium controls. The enhanced transcriptional activity of GSTP1 and GSTT2 genes was confirmed with real-time qRT-PCR. On the basis of the pattern of differential gene expression found here, we conclude that apple flavonoids modulate toxicological defense against colon cancer risk factors. In addition to the inhibition of tumor cell proliferation, this could be a mechanism of cancer risk reduction. © 2005 Wiley-Liss, Inc.

Deepthi Menon - One of the best experts on this subject based on the ideXlab platform.

  • glutathione transferases regulators of cellular metabolism and physiology
    Biochimica et Biophysica Acta, 2013
    Co-Authors: Philip G. Board, Deepthi Menon
    Abstract:

    Abstract Background The cytosolic glutathione transferases (GSTs) comprise a super family of proteins that can be categorized into multiple classes with a mixture of highly specific and overlapping functions. Scope of review The review covers the genetics, structure and function of the human cytosolic GSTs with particular attention to their emerging roles in cellular metabolism. Major conclusions All the catalytically active GSTs contribute to the glutathione conjugation or glutathione dependant-Biotransformation of Xenobiotics and many catalyze glutathione peroxidase or thiol transferase reactions. GSTs also catalyze glutathione dependent isomerization reactions required for the synthesis of several prostaglandins and steroid hormones and the catabolism of tyrosine. An increasing body of work has implicated several GSTs in the regulation of cell signaling pathways mediated by stress-activated kinases like Jun N-terminal kinase. In addition, some members of the cytosolic GST family have been shown to form ion channels in intracellular membranes and to modulate ryanodine receptor Ca2 + channels in skeletal and cardiac muscle. General significance In addition to their well established roles in the conjugation and Biotransformation of Xenobiotics, GSTs have emerged as significant regulators of pathways determining cell proliferation and survival and as regulators of ryanodine receptors that are essential for muscle function. This article is part of a Special Issue entitled Cellular functions of glutathione.