FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2959575917> ?p ?o ?g. }

• W2959575917 abstract "Polycyclic aromatic hydrocarbons (PAH´s) represent a class of substances formed in all types of incomplete combustion of organic compounds. Some of its members have - due to certain molecular structure chracteristics –  procarcinogenic properties in both man and laboratory animals. PAH´s are metabolized within the organism by the almost ubiquitous classes of cytochrome P450 enzymes and epoxide hydrolases (functionalization, phase 1) and sulfotransferases, UDP-glucuronosyltransferases and glutathione-S-transferases (conjugation, phase 2). The enzymatic reactions of phase 1 result in an increased reactivity with cellular macromolecules (including DNA), but are also the prerequisite for phase 2 reactions which increase the molecules´ hydrophilicity decisively, enabling the organism to excrete the PAH´s via the kidney, the bile and (as recently shown for the carcinogenic PAH benzo[a]pyrene) the intestinal mucosa. In the present work, the existence of a biphasic metabolism and a subsequent metabolite transport via the intestinal epithelium was examined and demonstrated for the noncarcinogenic PAH pyrene, including the identification of the participating enzymes, their products and the proteins involved in the transport. The human intestinal cell line Caco-2 was chosen as a model for the intestinal epithelium by reason of its close similarity (in morphology and  cellular biochemistry) with small bowel enterocytes. The ability of different human sulfotransferases to metabolize pyrene and pyrene-1-hydroxide was examined in the hamster cell line V79, the role of the transport protein cMOAT/MRP2 in the metabolite transport was investigated using the canine cell line MDCK II. The results can be summarized as follows: 1.      In Caco-2 cells, pyrene is metabolized to pyrene-1-hydroxide (phase 1). 2.      The hydroxilation of pyrene is carried out mainly by the cytochromes P450 1A1, P450 1A2 and/or P450 1B1. This reaction is inducible by several CYP1A1 inductors and can be inhibited by α-naphtoflavone, an inhibitor of CYP1A1, CYP1A2 and CYP1B1. 3.      Pyrene-1-hydroxide is metabolized by Caco-2 cells to pyrene-1-glucuronide and pyrene-1-sulfate. 4.       Pyrene-1-hydroxide is a substrate for the human sulfotransferases hSULT1A2*1, hSULT1A1*Arg, hSULT1A3 and hSULT1B1. 5.      Pyrene-1-sulfate formed in the cytosol is transported by Caco-2 cells in a directed manner across the apical cytoplasma membrane, unless a pharmacological inhibition of transport proteins is imposed. 6.      The results indicate that pyrene-1-glucuronide, too, is subjected to a directed transport into the apical direction. Pyrene and pyrene-1-hydroxide, however, are not transported in a directed way.                                                                       7.      The transport protein cMOAT/MRP2 does not transport pyrene-1-sulfate. 8.      Pyrene-1-sulfate (and, presumably, also pyrene-1-glucuronide) are substrates of the ABC transport protein BCRP that is also expressed in intestinal cells in vivo. The direction of pyrene-1-sulfate (and, as indicated by the experimental results, also pyrene-1-glucuronide) transport is reversed using Ko 143, an inhibitor of this transport protein. 9.      Pyrene and its metabolites formed in Caco-2 cells do not induce the mRNA expression of CYP1A1, CYP1B1, hSULT1A1, hSULT1B1, UGT1A6 and the transmembrane transport proteins p-glycoprotein and cMOAT/MRP2. A metabolization of pyrene following the aforementioned metabolic pathways can also be postulated for the human small intestine. The interaction of metabolism and transport of PAH´s in the human intestinal mucosa is not limited to the carcinogenic members of the PAH class, even though pyrene, unlike many carcinogenic PAH´s, does not induce its own phase 1- and phase 2 metabolism. Notably, the differences between the amounts of pyrene-1-sulfate transported into the apical and basolateral directions are less distinct than those for benzo[a]pyrene-1- and –3-sulfate, these two compounds  being transported much more efficiently into the apical direction by Caco-2 cells  under similar experimental conditions (BUSEN et al., 2002). This indicates a lower affinity of the apical transport protein(s) for the pyrene metabolite in comparison with the corresponding conjugated metabolites of carcinogenic PAH´s like benzo[a]pyrene, or, in other words, an optimization of protection against carcinogens." @default.
• W2959575917 created "2019-07-23" @default.
• W2959575917 creator A5069008109 @default.
• W2959575917 date "2004-01-01" @default.
• W2959575917 modified "2023-09-27" @default.
• W2959575917 title "Interaktion zwischen Metabolismus und Transport von Pyren in Caco-2-Zellen als Modell der gastrointestinalen Barriere" @default.
• W2959575917 cites W119204785 @default.
• W2959575917 cites W1513330739 @default.
• W2959575917 cites W153428855 @default.
• W2959575917 cites W1545611675 @default.
• W2959575917 cites W1546135534 @default.
• W2959575917 cites W1547018882 @default.
• W2959575917 cites W1556464588 @default.
• W2959575917 cites W1558112674 @default.
• W2959575917 cites W1572786475 @default.
• W2959575917 cites W1624721816 @default.
• W2959575917 cites W1628890212 @default.
• W2959575917 cites W1768069605 @default.
• W2959575917 cites W1787076927 @default.
• W2959575917 cites W1787401899 @default.
• W2959575917 cites W1849763436 @default.
• W2959575917 cites W1875161015 @default.
• W2959575917 cites W1892194801 @default.
• W2959575917 cites W1894354685 @default.
• W2959575917 cites W1910056530 @default.
• W2959575917 cites W1911655428 @default.
• W2959575917 cites W1923734449 @default.
• W2959575917 cites W1943747111 @default.
• W2959575917 cites W1949646639 @default.
• W2959575917 cites W1964470226 @default.
• W2959575917 cites W1967914030 @default.
• W2959575917 cites W1976917904 @default.
• W2959575917 cites W198065351 @default.
• W2959575917 cites W1984251825 @default.
• W2959575917 cites W1984613701 @default.
• W2959575917 cites W1989270171 @default.
• W2959575917 cites W1993115973 @default.
• W2959575917 cites W1995131475 @default.
• W2959575917 cites W1996632591 @default.
• W2959575917 cites W1999885398 @default.
• W2959575917 cites W2012841076 @default.
• W2959575917 cites W2019372916 @default.
• W2959575917 cites W2019605110 @default.
• W2959575917 cites W2024587809 @default.
• W2959575917 cites W2025033304 @default.
• W2959575917 cites W2026658540 @default.
• W2959575917 cites W2028273867 @default.
• W2959575917 cites W2028603080 @default.
• W2959575917 cites W2038583974 @default.
• W2959575917 cites W2040716003 @default.
• W2959575917 cites W2051727820 @default.
• W2959575917 cites W2052209393 @default.
• W2959575917 cites W2053613458 @default.
• W2959575917 cites W2054457316 @default.
• W2959575917 cites W2055552041 @default.
• W2959575917 cites W2056627798 @default.
• W2959575917 cites W2060674357 @default.
• W2959575917 cites W206710202 @default.
• W2959575917 cites W2067493329 @default.
• W2959575917 cites W2067615424 @default.
• W2959575917 cites W2072010935 @default.
• W2959575917 cites W2072682236 @default.
• W2959575917 cites W2078877172 @default.
• W2959575917 cites W2082524899 @default.
• W2959575917 cites W2083468617 @default.
• W2959575917 cites W2083715780 @default.
• W2959575917 cites W2084311588 @default.
• W2959575917 cites W2086419451 @default.
• W2959575917 cites W2086695517 @default.
• W2959575917 cites W2087552598 @default.
• W2959575917 cites W2089118929 @default.
• W2959575917 cites W2091239909 @default.
• W2959575917 cites W2095060296 @default.
• W2959575917 cites W2101564676 @default.
• W2959575917 cites W2110575867 @default.
• W2959575917 cites W2110790042 @default.
• W2959575917 cites W2117927958 @default.
• W2959575917 cites W2118234018 @default.
• W2959575917 cites W2124739658 @default.
• W2959575917 cites W2126921546 @default.
• W2959575917 cites W2131504112 @default.
• W2959575917 cites W2132452783 @default.
• W2959575917 cites W2134812217 @default.
• W2959575917 cites W2142024216 @default.
• W2959575917 cites W2146909058 @default.
• W2959575917 cites W2150342479 @default.
• W2959575917 cites W2152539673 @default.
• W2959575917 cites W2154661467 @default.
• W2959575917 cites W2157466663 @default.
• W2959575917 cites W2162740038 @default.
• W2959575917 cites W2169842884 @default.
• W2959575917 cites W2170643981 @default.
• W2959575917 cites W2182875022 @default.
• W2959575917 cites W2187718168 @default.
• W2959575917 cites W2249561773 @default.
• W2959575917 cites W2264818022 @default.
• W2959575917 cites W2289618010 @default.
• W2959575917 cites W2305603634 @default.
• W2959575917 cites W2326620573 @default.
• W2959575917 cites W2419540374 @default.

• next