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Wyświetlanie 1-3 z 3
Tytuł:
Phenobarbital-induced expression of cytochrome P450 genes.
Autorzy:
Czekaj, Piotr
Powiązania:
https://bibliotekanauki.pl/articles/1044233.pdf
Data publikacji:
2000
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
CYP2B
cytochrome P450
phenobarbital-responsive enhancer unit
CYP2H1.
orphan receptors
CYP3A
PXR
CAR
phenobarbital
Opis:
In contrast to the well-known Ah receptor-mediated regulation of the CYP1A1 gene by polycyclic aromatic hydrocarbons, the molecular mechanism by which phenobarbital (PB) and PB-like inducers affect transcription of CYP genes remains unknown; no receptor for these chemicals has been found to date. However, in the last 5 years PB-responsive sequences have been identified in the 5' flanking regions of several P450 genes. The phenobarbital-responsive enhancer unit (PBRU) of CYP2B gene family members contain two potential nuclear receptor binding sites (NR1 and NR2) that flank a nuclear factor 1 (NF-1) binding motif. The nuclear factors that regulate PBRU activity have not yet been characterized. It seems that PB may activate multiple nuclear orphan receptors to induce various CYP genes. CYP2B and CYP3A genes appear to be targets for the orphan receptors CAR and PXR, respectively. It is also possible that the pleiotropic effects of PB can, in part, be explained by the ability of the CAR-RXR heterodimer to bind to a variety of nuclear receptor binding motifs. The induction of cytochromes P450 may result in interactions between xenobiotics and in the interference of xenobiotic metabolism and endogenous signalling pathways.
Źródło:
Acta Biochimica Polonica; 2000, 47, 4; 1093-1105
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Expression of cytochrome P450 2C and 3A in female rat liver after long-term administration of gonadoliberin analogs
Autorzy:
Skowronek, Rafał
Czekaj, Piotr
Suszka-Świtek, Aleksandra
Czech, Ewa
Wiaderkiewicz, Anna
Plewka, Danuta
Bryzek, Aleksandra
Powiązania:
https://bibliotekanauki.pl/articles/2177070.pdf
Data publikacji:
2015-11-27
Wydawca:
Instytut Medycyny Pracy im. prof. dra Jerzego Nofera w Łodzi
Tematy:
CYP2C
CYP3A
liver-enriched transcription factors
growth hormone
dalarelin
cetrorelix
Opis:
Objectives Gonadoliberin (GnRH) analogs may be expected to indirectly modify growth hormone (GH) total concentration and its 24-h secretion profile. As a consequence, changes in the levels of GH may modify the mechanism of sexdependent cytochromes P450 (CYP450) synthesis, including the expression of transcriptional factors. The aim of the study has been to evaluate the effect of long-term administration of a low dose of GnRH analogs on hepatic expression of CYP2C and CYP3A isoforms, and the transcription factors: pregnane X receptor (PXR), hepatocyte nuclear factor 4α (HNF4α), HNF6 and signal transducers and activators of transcription 5b (STAT5b). Material and Methods The study was carried out on adult female Sprague-Dawley rats during a 3-month treatment with dalarelin (GnRH agonist) and cetrorelix (GnRH antagonist), at a daily intraperitoneal injection (i.p.) dose of 6 μg/kg body weight/day, and 1, 2, and 4 weeks after treatment discontinuation. The concentrations of ovarian hormones and GH in the blood serum were determined by radioimmunoassay and enzyme-linked immunosorbent assay (ELISA) method, respectively. Then, the expression of hepatic CYP450s (reverse transcription polymerase chain reaction – RT-PCR, Western blot and immunohistochemistry) and transcription factors (RT-PCR) was evaluated. Results We have found that cetrorelix induces changes in the circadian pattern of GH secretion and enhances GH blood concentrations. These changes may cause increased expression of both, female-specific CYP450s (especially CYP3A9), and HNF4α/HNF6 transcription factors. Decrease in GH blood concentrations, resulting from the effect of dalarelin, may promote inhibition of female-specific CYP2C12 and CYP3A9 isoforms as well as STAT5b transcription factor. Slight changes in sex-independent CYP3A1 protein expression caused by GnRH analogs were also observed. Conclusions In adult female rats, HNF4α/HNF6 and STAT5b seem to be crucial for the regulation of GnRH antagonist/GH- and GnRH agonist/GH-dependent pattern of CYP450 expression, respectively.
Źródło:
International Journal of Occupational Medicine and Environmental Health; 2016, 29, 2; 293-314
1232-1087
1896-494X
Pojawia się w:
International Journal of Occupational Medicine and Environmental Health
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Expression of cytochrome CYP2B1/2 in nonpregnant, pregnant and fetal rats exposed to tobacco smoke.
Autorzy:
Czekaj, Piotr
Wiaderkiewicz, Anna
Florek, Ewa
Wiaderkiewicz, Ryszard
Powiązania:
https://bibliotekanauki.pl/articles/1044235.pdf
Data publikacji:
2000
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
pregnancy
CYP2B6
rats
cytochrome P450
CYP2B1/2
tobacco smoke
Opis:
Four-month-old female Wistar rats were exposed for 20 days to tobacco smoke obtained from non-filter cigarettes. During the exposure, concentration of tobacco smoke was monitored indirectly by measuring the CO level (1500 mg/m3 air). The efficacy of exposure was assessed by measuring urine nicotine and cotinine levels. Cigarette smoke did not change total cytochrome P450 and b5 protein levels in any of the organs studied, and most of these organs did not show any changes in the activity of reductases associated with these cytochromes. Following exposure to tobacco smoke, fetal rat liver expressed CYP2B1/2 protein; in newborns (day 1) both liver and lung showed CYP2B1/2 protein expression and very low pentoxyresorufin O-dealkylase activity. Western blot analysis of adult liver, lung, heart, but not of brain microsomes, showed that tobacco smoke induced CYP2B1/2 in both nonpregnant and pregnant rats, though its expression was lower in the livers and hearts of pregnant females. In the rat and human placenta, neither rat CYP2B1/2 nor human CYP2B6 showed basal or tobacco smoke-induced expression at the protein level. This study shows clearly that the expression of CYP2B1/2, which metabolizes nicotine and some drugs and activates carcinogens, is controlled in rats by age-, pregnancy-, and tissue-specific regulatory mechanisms.
Źródło:
Acta Biochimica Polonica; 2000, 47, 4; 1115-1127
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
    Wyświetlanie 1-3 z 3

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