Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
The gene expression profile of a drug metabolism system and signal transduction pathways in the liver of mice treated with tertbutylhydroquinone or 3-(3'-tert-butyl-4'- hydroxyphenyl)propylthiosulfonate of sodium. / Shintyapina, Alexandra B.; Vavilin, Valentin A.; Safronova, Olga G. и др.
в: PLoS ONE, Том 12, № 5, 0176939, 01.05.2017, стр. e0176939.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - The gene expression profile of a drug metabolism system and signal transduction pathways in the liver of mice treated with tertbutylhydroquinone or 3-(3'-tert-butyl-4'- hydroxyphenyl)propylthiosulfonate of sodium
AU - Shintyapina, Alexandra B.
AU - Vavilin, Valentin A.
AU - Safronova, Olga G.
AU - Lyakhovich, Vyacheslav V.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Tert-butylhydroquinone (tBHQ) is a highly effective phenolic antioxidant used in edible oils and fats in foods as well as in medicines and cosmetics. TBHQ has been shown to have both chemoprotective and carcinogenic effects. Furthermore, it has potential anti-inflammatory, antiatherogenic, and neuroprotective activities. TBHQ induces phase II detoxification enzymes via the Keap1/Nrf2/ARE mechanism, which contributes to its chemopreventive functions. Nonetheless, there is growing evidence that biological effects of tBHQ may be mediated by Nrf2-independent mechanisms related to various signaling cascades. Here, we studied changes in gene expression of phase I, II, and III drug metabolizing enzymes/transporters as well as protein levels and activities of cytochromes P450 (CYPs) elicited by tBHQ and its structural homolog TS-13 in the mouse liver. Next, we carried out gene expression analysis to identify signal transduction pathways modulated by the antioxidants. Mice received 100 mg/kg tBHQ or TS-13 per day or only vehicle. The liver was collected at 12 hours and after 7 days of the treatment. Protein and total RNA were extracted. Gene expression was analyzed using Mouse Drug Metabolism and Signal Transduction PathwayFinder RT2Profiler PCR Arrays. A western blot analysis was used to measure protein levels and a fluorometric assay was employed to study activities of CYPs. Genes that were affected more than 1.5-fold by tBHQ or TS-13 treatment compared with vehicle were identified. Analysis of the gene expression data revealed changes in various genes that are important for drug metabolism, cellular defense mechanisms, inflammation, apoptosis, and cell cycle regulation. Novel target genes were identified, including xenobiotic metabolism genes encoding CYPs, phase II/III drug metabolizing enzymes/transporters. For Cyp1a2 and Cyp2b, we observed an increase in protein levels and activities during tBHQ or TS-13 treatment. Changes were found in the gene expression regulated by NFκB, androgen, retinoic acid, PI3K/AKT, Wnt, Hedgehog and other pathways.
AB - Tert-butylhydroquinone (tBHQ) is a highly effective phenolic antioxidant used in edible oils and fats in foods as well as in medicines and cosmetics. TBHQ has been shown to have both chemoprotective and carcinogenic effects. Furthermore, it has potential anti-inflammatory, antiatherogenic, and neuroprotective activities. TBHQ induces phase II detoxification enzymes via the Keap1/Nrf2/ARE mechanism, which contributes to its chemopreventive functions. Nonetheless, there is growing evidence that biological effects of tBHQ may be mediated by Nrf2-independent mechanisms related to various signaling cascades. Here, we studied changes in gene expression of phase I, II, and III drug metabolizing enzymes/transporters as well as protein levels and activities of cytochromes P450 (CYPs) elicited by tBHQ and its structural homolog TS-13 in the mouse liver. Next, we carried out gene expression analysis to identify signal transduction pathways modulated by the antioxidants. Mice received 100 mg/kg tBHQ or TS-13 per day or only vehicle. The liver was collected at 12 hours and after 7 days of the treatment. Protein and total RNA were extracted. Gene expression was analyzed using Mouse Drug Metabolism and Signal Transduction PathwayFinder RT2Profiler PCR Arrays. A western blot analysis was used to measure protein levels and a fluorometric assay was employed to study activities of CYPs. Genes that were affected more than 1.5-fold by tBHQ or TS-13 treatment compared with vehicle were identified. Analysis of the gene expression data revealed changes in various genes that are important for drug metabolism, cellular defense mechanisms, inflammation, apoptosis, and cell cycle regulation. Novel target genes were identified, including xenobiotic metabolism genes encoding CYPs, phase II/III drug metabolizing enzymes/transporters. For Cyp1a2 and Cyp2b, we observed an increase in protein levels and activities during tBHQ or TS-13 treatment. Changes were found in the gene expression regulated by NFκB, androgen, retinoic acid, PI3K/AKT, Wnt, Hedgehog and other pathways.
KW - Animals
KW - Blotting, Western
KW - Cytochrome P-450 Enzyme System/metabolism
KW - Hydroquinones/pharmacology
KW - Inactivation, Metabolic/drug effects
KW - Liver/drug effects
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Microsomes, Liver/drug effects
KW - Real-Time Polymerase Chain Reaction
KW - Signal Transduction/drug effects
KW - Thiosulfonic Acids/pharmacology
KW - Transcriptome/drug effects
KW - HUMAN NEUROBLASTOMA-CELLS
KW - OXIDATIVE STRESS
KW - ACTIVATED PROTEIN-KINASE
KW - INDUCED APOPTOSIS
KW - PHOSPHATIDYLINOSITOL 3-KINASE
KW - ANTIOXIDANT-RESPONSIVE ELEMENT
KW - CONSTITUTIVE ANDROSTANE RECEPTOR
KW - COORDINATE REGULATION
KW - INFLAMMATORY RESPONSE
KW - NF-KAPPA-B
UR - http://www.scopus.com/inward/record.url?scp=85018760614&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0176939
DO - 10.1371/journal.pone.0176939
M3 - Article
C2 - 28467491
AN - SCOPUS:85018760614
VL - 12
SP - e0176939
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 5
M1 - 0176939
ER -
ID: 10256697