Dehydroepiandrosterone post-transcriptionally modifies CYP1A2 induction involving androgen receptor.
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Type = Article
Cím:
Dehydroepiandrosterone post-transcriptionally modifies CYP1A2 induction involving androgen receptor.
Létrehozó:
Belic, Ales
Tóth, Katalin
Vrzal, Radim
Temesvári, Manna
Porrogi, Pálma
Monostory, Katalin
Dvorak, Zdenek
Orbán, Erika
Rozman, Damjana
Kiadó:
Elsevier
Dátum:
2013
Téma:
QD Chemistry / kémia
RS Pharmacy and materia medica / gyógyszerészet, gyógyászati eszközök
Tartalmi leírás:
The pharmacological dosage of dehydroepiandrosterone (DHEA) protects against chemically
induced carcinogenesis. The chemoprotective activity of DHEA is attributed to its inhibitory
potential for the expression of CYP1A enzymes, which are highly responsible for metabolic
activation of several mutagenic and carcinogenic chemicals. The present work investigated
whether the chemoprevention by DHEA was due to diminished transcriptional activation of
CYP1A genes or to the post-transcriptional modulation of CYP1A expression. In primary human hepatocytes, DHEA diminished the increase in CYP1A activities
(7-ethoxyresorufin O-dealkylation and phenacetin O-dealkylation) and in CYP1A2 mRNA
level induced by 3-methylcholanthrene, but did not alter the amount of CYP1A1 and CYP1B1
mRNA. The androgen receptor seemed to be involved in DHEA-mediated diminishment of
CYP1A2 induction, which was attenuated in the presence of bicalutamide, the androgen
receptor antagonist. The potential role of the glucocorticoid receptor and estrogen receptor in
DHEA-mediated decrease in CYP1A2 induction was excluded. The developed computational
model of CYP1A2 induction kinetics and CYP1A2 mRNA degradation proposed that a posttranscriptional
mechanism was likely to be the primary mechanism of the DHEA-mediated
diminishment of CYP1A2 induction. The hypothesis was confirmed by the results of
actinomycin D-chase experiments in MCF-7 and LNCaP cells, displaying that the degradation
rates of CYP1A2 mRNA were significantly higher in the cells exposed to DHEA. The novel findings on DHEA-mediated modulation of CYP1A2 mRNA stability may
account for the beneficial effects of DHEA by decreasing the metabolic activation of procarcinogenic
compounds.
Típus:
Article
PeerReviewed
Formátum:
text
Azonosító:
Belic, Ales and Tóth, Katalin and Vrzal, Radim and Temesvári, Manna and Porrogi, Pálma and Monostory, Katalin and Dvorak, Zdenek and Orbán, Erika and Rozman, Damjana (2013) Dehydroepiandrosterone post-transcriptionally modifies CYP1A2 induction involving androgen receptor. CHEMICO-BIOLOGICAL INTERACTIONS, 203 (3). pp. 597-603. ISSN 0009-2797
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