Vladimir Pustylnyak | Novosibirsk State University (original) (raw)

Papers by Vladimir Pustylnyak

Archives of Biochemistry and Biophysics

Recently, we reported that treatment with the mouse agonist of the constitutive androstane recept... more Recently, we reported that treatment with the mouse agonist of the constitutive androstane receptor (CAR), 1,4-bis benzene[2-(3,5-dichloropyridyloxy)] (TCPOBOP; a well-known hepatomitogen), reduced PTEN protein levels, leading to Akt activation. Hence, the present study was performed to demonstrate the role of CAR in PTEN regulation and liver growth. Liver hyperplasia caused by CAR activation was confirmed to be mediated by a decrease in PTEN protein level and the activation of the Akt signalling pathway in the liver of mice. Treatment with the CAR agonist decreased the PTEN levels and increased Foxm1 levels, which correlate with the elevated expression of the FoxM1 target gene, Nedd4-1, an E3 ligase involved in PTEN ubiquitination, and the promotion of degradation. The increase in Nedd4-1 levels was accompanied by an increase in CAR-mediated accumulation of Foxm1 on the Nedd4-1 gene promoter. Therefore, these results provide evidence that a notable function of CAR is its liver growth promotion effect, which is accompanied by FoxM1-Nedd4-mediated repression of PTEN and Akt pathway activation.

European journal of pharmacology, Jan 15, 2017

Although NR1C3 agonists inhibit cell growth, the molecular mechanism of their action has not been... more Although NR1C3 agonists inhibit cell growth, the molecular mechanism of their action has not been thoroughly characterized to date. A recent study demonstrated that NR1C3 can regulate miR-122 by binding to its promoter. Given that miR-122 can indirectly regulate cMyc-mediated promitogenic signaling by targeting E2f1, we hypothesized that NR1C3 activation inhibits hepatocyte proliferation through miR-122-mediated cMyc downregulation. In the present study, we examined if liver hyperplasia induced by a strong chemical mitogen for the liver, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of NR1I3, can be repressed by NR1C3 activation through miR-122 upregulation. Acute TCPOBOP treatment caused a significant increase in liver-to-body weight ratio. The liver mass increase was accompanied with miR-122 downregulation. ChIP assays demonstrated that TCPOBOP-activated NR1I3 accumulated on the DR1 site in the pri-miR-122 promoter; and the NR1I3 accumulation is accompa...

European Journal of Pharmacology

Gene, Jan 20, 2018

The effects of microRNAs on PTEN levels are characteristic for many types of cancer. However, the... more The effects of microRNAs on PTEN levels are characteristic for many types of cancer. However, the picture of the correlation between the expression levels of PTEN and its targeting microRNAs in endometrial cancer is not fully presented. Our study investigated and analysed the expression levels of PTEN and PTEN-targeting miR-21, miR-181a, miR-214, miR-301a, and miR-1908 in total of 78 samples, out of which 26 samples were from normal endometrium, whereas the 52 samples were from endometrial cancer samples. Our results demonstrated a high variability of individual endometrial cancer samples in the levels of PTEN. The level of miR-181a showed significant increment in endometrial cancer tissues in comparison with normal endometrium. We did not observe any statistically significant correlation between levels of microRNAs and PTEN in a heterogeneous cohort of patients. At the same time, in samples collected from endometrial cancer patients, it was found out that the relationship between P...

Journal of Cancer, 2018

Identification of prognostic molecular markers of breast cancer is extremely important. The sprea... more Identification of prognostic molecular markers of breast cancer is extremely important. The spreading out of the primary breast tumour cells to the lymphatic system is at the forefront of symbolising the first signs of distant organ metastasis. Deregulated genes in breast cancer tissues that spread to lymph nodes may show early predictive molecular markers. In the present study, we selected five microRNAs, which play a key function in the invasion-metastasis cascade. We investigated the levels of microRNAs in 80 paired samples of BC and matched adjoining tissues, and we examined the potential relationships between microRNA levels and positive lymph node status. Our results attest that three microRNAs (miR-21, miR-155, miR-222) were significantly up-regulated, whilst miR-205 was substantially down-regulated in BC tissues in relation to normal adjoining tissues in a heterogeneous patient cohort. The high levels of two microRNAs, miR-155 and miR-222, showed a statistical relation with ...

European Journal of Pharmacology

Biochemical and Biophysical Research Communications

It is well-known that constitutive androstane receptor (CAR) activation by 1,4-bis[2-(3,5-dichlor... more It is well-known that constitutive androstane receptor (CAR) activation by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) increases the liver-to-body weight ratio. CAR-mediated liver growth is correlated with increased expression of the pleiotropic transcription factor cMyc, which stimulates cell cycle regulatory genes and drives proliferating cells into S phase. Because glycolysis supports cell proliferation and cMyc is essential for the activation of glycolytic genes, we hypothesized that CAR-mediated up-regulation of cMyc in mouse livers might play a role in inducing the expression of glycolytic genes. The aim of the present study was to examine the effect of long-term CAR activation on glycolytic genes in a mouse model not subjected to metabolic stress. We demonstrated that long-term CAR activation by TCPOBOP increases expression of cMyc, which was correlated with reduced expression of gluconeogenic genes and up-regulation of glucose transporter, glycolytic and mitochondrial pyruvate metabolising genes. These changes in gene expression after TCPOBOP treatment were strongly correlated with changes in levels of glycolytic intermediates in mouse livers. Moreover, we demonstrated a significant positive regulatory effect of TCPOBOP-activated CAR on both mRNA and protein levels of Pkm2, a master regulator of glucose metabolism and cell proliferation. Thus, our findings provide evidence to support the conclusion that CAR activation initiates a transcriptional program that facilitates the coordinated metabolic activities required for cell proliferation.

International Journal of Molecular Sciences

The constitutive androstane receptor (CAR, NR1I3) is extremely important for the regulation of ma... more The constitutive androstane receptor (CAR, NR1I3) is extremely important for the regulation of many physiological processes, especially xenobiotic (drug) metabolism and transporters. CAR differs from steroid hormone receptors in that it can be activated using structurally unrelated chemicals, both through direct ligand-binding and ligand-independent (indirect) mechanisms. By binding to specific responsive elements on DNA, CAR increases the expression of its target genes encoding drug-metabolizing enzymes and transporters. Therefore, CAR is mainly characterized as a ligand-dependent or ligand-independent transcription factor, and the induction of gene expression is considered the canonical mode of CAR action. Consistent with its central role in xenobiotic metabolism, CAR signaling includes a collection of mechanisms that are employed alongside the core transcriptional machinery of the receptor. These so-called noncanonical CAR pathways allow the receptor to coordinate the regulation ...

Bulletin of Experimental Biology and Medicine, 2009

The expression of egr-1, junB, c-jun, and c-fos genes in rat hippocampal CA1 field was studied by... more The expression of egr-1, junB, c-jun, and c-fos genes in rat hippocampal CA1 field was studied by the real-time PCR 30, 60, and 120 min after induction of long-term posttetanic potentiation. The content of egr-1, junB, and c-jun mRNA gradually increased and doubled 120 min after tetanization. The increase in c-jun mRNA level lagged behind the increment of egr-1 and junB. The level of c-fos mRNA increased 30 min after tetanization, returned to the initial level by min 60, and again increased 120 min after induction of long-term posttetanic potentiation.

Bulletin of experimental biology and medicine, 2014

Expression of Bcl2 family genes was studied during the early phase of long-term potentiation in t... more Expression of Bcl2 family genes was studied during the early phase of long-term potentiation in the CA1 field of rat hippocampal slices. The level of Bax mRNA and protein increased, while the content of Bcl2 mRNA and protein decreased 30 min after tetanization of the Schaffer collaterals. Our results suggest that proteins of the Bcl2 family play a role in the mechanisms of synaptic plasticity.

Bulletin of Experimental Biology and Medicine, 2013

The effects of NMDA receptor blocker MK-801 on the increase in S100B protein mRNA content induced... more The effects of NMDA receptor blocker MK-801 on the increase in S100B protein mRNA content induced by long-term posttetanic potentiation in the hippocampal sections were studied. The level of S100B mRNA after 30-min tetanization in the presence of 10 μM MK-801 constituted 132% of the basal level, which was significantly (226%) lower than the control level. Hence, gene expression, induced by long-term posttetanic potentiation, in the glial cells (similarly as in the neurons) depended significantly on NMDA receptors.

Neuroscience and Behavioral Physiology, 2016

Bulletin of Experimental Biology and Medicine, 2016

Bulletin of Experimental Biology and Medicine, 2009

The expression of S100B and S100A6 mRNA in CA1 region of rat hippocampal sections was studied aft... more The expression of S100B and S100A6 mRNA in CA1 region of rat hippocampal sections was studied after tetanizing stimulation. The level of S100B expression increased 2-4-fold in comparison with the control after 30 min and gradually returned to the basal level 120 min after tetanization. The level of S100A6 mRNA was very low and did not change after tetanization.

Toxicology and Applied Pharmacology, 2015

MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA popula... more MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter. Pri-miR-122 expression is regulated by liver-enriched transcription factors, mainly by HNF4α, which mediates the expression via the interaction with a specific DR1 site. It has been shown that phenobarbital-mediated activation of constitutive androstane receptor (CAR), xenobiotic nuclear receptor, is associated with a decrease in miR-122 in the liver. In the present study, we investigated HNF4α-CAR cross-talk in the regulation of miR-122 levels and promitogenic signalling in mouse livers. The level of miR-122 was significantly repressed by treatment with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of mouse CAR. ChIP assays demonstrated that TCPOBOP-activated CAR inhibited HNF4α transactivation by competing with HNF4α for binding to the DR1 site in the pri-miR-122 promoter. Such transcription factor replacement was strongly correlated with miR-122 down-regulation. Additionally, the decrease in miR-122 levels produced by CAR activation is accompanied by an increase in mRNA and cellular protein levels of E2f1 and its accumulation on the target cMyc gene promoter. The increase in accumulation of E2f1 on the target cMyc gene promoter is accompanied by an increase in cMyc levels and transcriptional activity. Thus, our results provide evidence to support the conclusion that CAR activation decreases miR-122 levels through suppression of HNF4α transcriptional activity and indirectly regulates the promitogenic protein cMyc. HNF4α-CAR cross-talk may provide new opportunities for understanding liver diseases and developing more effective therapeutic approaches to better drug treatments.

Many xenobiotics are capable of cytochrome P450 induction. In many cases this process occurs via ... more Many xenobiotics are capable of cytochrome P450 induction. In many cases this process occurs via the interaction with specific nuclear receptors (CAR, AhR, PXR). There is a large group of structurally diverse chemicals (PB-like inducers) which activate gene transcription of CYP2B and CYP3A in species- and tissue-specific manner. We have studied induction of these P450s by a specific inducer 2,4,6-triphenyldioxane-1,3 (TPD) and have shown that this compound induces CYP2B in rat liver via a transcriptional mechanism, but not in mouse liver. Moreover, TPD in contrast to phenobarbital specifically activates the Ca++-calmodulin-dependent signal transduction pathway followed by the activation of the CAR receptor. We carry out the synthesis of several analogs of TPD using a reaction with 1,3-diphenylpropane-1,3-diol and corresponding 4-substituted benzaldehydes to verify a hypothesis that minor changes in the inducer structure can cause major changes in induction abilities. The results of ...

2,4,6-Tryphenyldioxane-1,3 (TPD) is a highly effective species-specific inducer of CYP2Â in rats.... more 2,4,6-Tryphenyldioxane-1,3 (TPD) is a highly effective species-specific inducer of CYP2Â in rats. Several analogs of TPD were synthesized using a reaction with 1,3-diphenylpropane-1,3-diol and corresponding substituted benzaldehydes to verify a hypothesis that minor changes in the inducer structure can cause changes in induction abilities (R=H, cisTPD and transTPD; R=N(CH3)2, pDMA; R=NO2, pNO2; R=F, pF; R=OCH3, pMetO). Male Wistar rats were treated by TPD or its analogs (single injection of 10 mg/kg body weight in corn oil). In rat liver cisTPD and transTPD, pDMA, pNO2, pF administration significantly increased total CYP content (1.3 2.5 fold) and the level of PROD (12 20 fold), CYP2B specific activity, whereas pMetO did not have any effects. Western blot and real-time RT-PCR showed that the increase of PROD in liver is related to the high content of CYP2B proteins and paralleled the increase of CYP2B1 (10 43 fold) and CYP2B2 (8 26 fold) mRNAs. At the same time content of CYP2B prot...

Archives of Biochemistry and Biophysics

Recently, we reported that treatment with the mouse agonist of the constitutive androstane recept... more Recently, we reported that treatment with the mouse agonist of the constitutive androstane receptor (CAR), 1,4-bis benzene[2-(3,5-dichloropyridyloxy)] (TCPOBOP; a well-known hepatomitogen), reduced PTEN protein levels, leading to Akt activation. Hence, the present study was performed to demonstrate the role of CAR in PTEN regulation and liver growth. Liver hyperplasia caused by CAR activation was confirmed to be mediated by a decrease in PTEN protein level and the activation of the Akt signalling pathway in the liver of mice. Treatment with the CAR agonist decreased the PTEN levels and increased Foxm1 levels, which correlate with the elevated expression of the FoxM1 target gene, Nedd4-1, an E3 ligase involved in PTEN ubiquitination, and the promotion of degradation. The increase in Nedd4-1 levels was accompanied by an increase in CAR-mediated accumulation of Foxm1 on the Nedd4-1 gene promoter. Therefore, these results provide evidence that a notable function of CAR is its liver growth promotion effect, which is accompanied by FoxM1-Nedd4-mediated repression of PTEN and Akt pathway activation.

European journal of pharmacology, Jan 15, 2017

Although NR1C3 agonists inhibit cell growth, the molecular mechanism of their action has not been... more Although NR1C3 agonists inhibit cell growth, the molecular mechanism of their action has not been thoroughly characterized to date. A recent study demonstrated that NR1C3 can regulate miR-122 by binding to its promoter. Given that miR-122 can indirectly regulate cMyc-mediated promitogenic signaling by targeting E2f1, we hypothesized that NR1C3 activation inhibits hepatocyte proliferation through miR-122-mediated cMyc downregulation. In the present study, we examined if liver hyperplasia induced by a strong chemical mitogen for the liver, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of NR1I3, can be repressed by NR1C3 activation through miR-122 upregulation. Acute TCPOBOP treatment caused a significant increase in liver-to-body weight ratio. The liver mass increase was accompanied with miR-122 downregulation. ChIP assays demonstrated that TCPOBOP-activated NR1I3 accumulated on the DR1 site in the pri-miR-122 promoter; and the NR1I3 accumulation is accompa...

European Journal of Pharmacology

Gene, Jan 20, 2018

The effects of microRNAs on PTEN levels are characteristic for many types of cancer. However, the... more The effects of microRNAs on PTEN levels are characteristic for many types of cancer. However, the picture of the correlation between the expression levels of PTEN and its targeting microRNAs in endometrial cancer is not fully presented. Our study investigated and analysed the expression levels of PTEN and PTEN-targeting miR-21, miR-181a, miR-214, miR-301a, and miR-1908 in total of 78 samples, out of which 26 samples were from normal endometrium, whereas the 52 samples were from endometrial cancer samples. Our results demonstrated a high variability of individual endometrial cancer samples in the levels of PTEN. The level of miR-181a showed significant increment in endometrial cancer tissues in comparison with normal endometrium. We did not observe any statistically significant correlation between levels of microRNAs and PTEN in a heterogeneous cohort of patients. At the same time, in samples collected from endometrial cancer patients, it was found out that the relationship between P...

Journal of Cancer, 2018

Identification of prognostic molecular markers of breast cancer is extremely important. The sprea... more Identification of prognostic molecular markers of breast cancer is extremely important. The spreading out of the primary breast tumour cells to the lymphatic system is at the forefront of symbolising the first signs of distant organ metastasis. Deregulated genes in breast cancer tissues that spread to lymph nodes may show early predictive molecular markers. In the present study, we selected five microRNAs, which play a key function in the invasion-metastasis cascade. We investigated the levels of microRNAs in 80 paired samples of BC and matched adjoining tissues, and we examined the potential relationships between microRNA levels and positive lymph node status. Our results attest that three microRNAs (miR-21, miR-155, miR-222) were significantly up-regulated, whilst miR-205 was substantially down-regulated in BC tissues in relation to normal adjoining tissues in a heterogeneous patient cohort. The high levels of two microRNAs, miR-155 and miR-222, showed a statistical relation with ...

European Journal of Pharmacology

Biochemical and Biophysical Research Communications

It is well-known that constitutive androstane receptor (CAR) activation by 1,4-bis[2-(3,5-dichlor... more It is well-known that constitutive androstane receptor (CAR) activation by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) increases the liver-to-body weight ratio. CAR-mediated liver growth is correlated with increased expression of the pleiotropic transcription factor cMyc, which stimulates cell cycle regulatory genes and drives proliferating cells into S phase. Because glycolysis supports cell proliferation and cMyc is essential for the activation of glycolytic genes, we hypothesized that CAR-mediated up-regulation of cMyc in mouse livers might play a role in inducing the expression of glycolytic genes. The aim of the present study was to examine the effect of long-term CAR activation on glycolytic genes in a mouse model not subjected to metabolic stress. We demonstrated that long-term CAR activation by TCPOBOP increases expression of cMyc, which was correlated with reduced expression of gluconeogenic genes and up-regulation of glucose transporter, glycolytic and mitochondrial pyruvate metabolising genes. These changes in gene expression after TCPOBOP treatment were strongly correlated with changes in levels of glycolytic intermediates in mouse livers. Moreover, we demonstrated a significant positive regulatory effect of TCPOBOP-activated CAR on both mRNA and protein levels of Pkm2, a master regulator of glucose metabolism and cell proliferation. Thus, our findings provide evidence to support the conclusion that CAR activation initiates a transcriptional program that facilitates the coordinated metabolic activities required for cell proliferation.

International Journal of Molecular Sciences

The constitutive androstane receptor (CAR, NR1I3) is extremely important for the regulation of ma... more The constitutive androstane receptor (CAR, NR1I3) is extremely important for the regulation of many physiological processes, especially xenobiotic (drug) metabolism and transporters. CAR differs from steroid hormone receptors in that it can be activated using structurally unrelated chemicals, both through direct ligand-binding and ligand-independent (indirect) mechanisms. By binding to specific responsive elements on DNA, CAR increases the expression of its target genes encoding drug-metabolizing enzymes and transporters. Therefore, CAR is mainly characterized as a ligand-dependent or ligand-independent transcription factor, and the induction of gene expression is considered the canonical mode of CAR action. Consistent with its central role in xenobiotic metabolism, CAR signaling includes a collection of mechanisms that are employed alongside the core transcriptional machinery of the receptor. These so-called noncanonical CAR pathways allow the receptor to coordinate the regulation ...

Bulletin of Experimental Biology and Medicine, 2009

The expression of egr-1, junB, c-jun, and c-fos genes in rat hippocampal CA1 field was studied by... more The expression of egr-1, junB, c-jun, and c-fos genes in rat hippocampal CA1 field was studied by the real-time PCR 30, 60, and 120 min after induction of long-term posttetanic potentiation. The content of egr-1, junB, and c-jun mRNA gradually increased and doubled 120 min after tetanization. The increase in c-jun mRNA level lagged behind the increment of egr-1 and junB. The level of c-fos mRNA increased 30 min after tetanization, returned to the initial level by min 60, and again increased 120 min after induction of long-term posttetanic potentiation.

Bulletin of experimental biology and medicine, 2014

Expression of Bcl2 family genes was studied during the early phase of long-term potentiation in t... more Expression of Bcl2 family genes was studied during the early phase of long-term potentiation in the CA1 field of rat hippocampal slices. The level of Bax mRNA and protein increased, while the content of Bcl2 mRNA and protein decreased 30 min after tetanization of the Schaffer collaterals. Our results suggest that proteins of the Bcl2 family play a role in the mechanisms of synaptic plasticity.

Bulletin of Experimental Biology and Medicine, 2013

The effects of NMDA receptor blocker MK-801 on the increase in S100B protein mRNA content induced... more The effects of NMDA receptor blocker MK-801 on the increase in S100B protein mRNA content induced by long-term posttetanic potentiation in the hippocampal sections were studied. The level of S100B mRNA after 30-min tetanization in the presence of 10 μM MK-801 constituted 132% of the basal level, which was significantly (226%) lower than the control level. Hence, gene expression, induced by long-term posttetanic potentiation, in the glial cells (similarly as in the neurons) depended significantly on NMDA receptors.

Neuroscience and Behavioral Physiology, 2016

Bulletin of Experimental Biology and Medicine, 2016

Bulletin of Experimental Biology and Medicine, 2009

The expression of S100B and S100A6 mRNA in CA1 region of rat hippocampal sections was studied aft... more The expression of S100B and S100A6 mRNA in CA1 region of rat hippocampal sections was studied after tetanizing stimulation. The level of S100B expression increased 2-4-fold in comparison with the control after 30 min and gradually returned to the basal level 120 min after tetanization. The level of S100A6 mRNA was very low and did not change after tetanization.

Toxicology and Applied Pharmacology, 2015

MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA popula... more MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter. Pri-miR-122 expression is regulated by liver-enriched transcription factors, mainly by HNF4α, which mediates the expression via the interaction with a specific DR1 site. It has been shown that phenobarbital-mediated activation of constitutive androstane receptor (CAR), xenobiotic nuclear receptor, is associated with a decrease in miR-122 in the liver. In the present study, we investigated HNF4α-CAR cross-talk in the regulation of miR-122 levels and promitogenic signalling in mouse livers. The level of miR-122 was significantly repressed by treatment with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of mouse CAR. ChIP assays demonstrated that TCPOBOP-activated CAR inhibited HNF4α transactivation by competing with HNF4α for binding to the DR1 site in the pri-miR-122 promoter. Such transcription factor replacement was strongly correlated with miR-122 down-regulation. Additionally, the decrease in miR-122 levels produced by CAR activation is accompanied by an increase in mRNA and cellular protein levels of E2f1 and its accumulation on the target cMyc gene promoter. The increase in accumulation of E2f1 on the target cMyc gene promoter is accompanied by an increase in cMyc levels and transcriptional activity. Thus, our results provide evidence to support the conclusion that CAR activation decreases miR-122 levels through suppression of HNF4α transcriptional activity and indirectly regulates the promitogenic protein cMyc. HNF4α-CAR cross-talk may provide new opportunities for understanding liver diseases and developing more effective therapeutic approaches to better drug treatments.

Many xenobiotics are capable of cytochrome P450 induction. In many cases this process occurs via ... more Many xenobiotics are capable of cytochrome P450 induction. In many cases this process occurs via the interaction with specific nuclear receptors (CAR, AhR, PXR). There is a large group of structurally diverse chemicals (PB-like inducers) which activate gene transcription of CYP2B and CYP3A in species- and tissue-specific manner. We have studied induction of these P450s by a specific inducer 2,4,6-triphenyldioxane-1,3 (TPD) and have shown that this compound induces CYP2B in rat liver via a transcriptional mechanism, but not in mouse liver. Moreover, TPD in contrast to phenobarbital specifically activates the Ca++-calmodulin-dependent signal transduction pathway followed by the activation of the CAR receptor. We carry out the synthesis of several analogs of TPD using a reaction with 1,3-diphenylpropane-1,3-diol and corresponding 4-substituted benzaldehydes to verify a hypothesis that minor changes in the inducer structure can cause major changes in induction abilities. The results of ...

2,4,6-Tryphenyldioxane-1,3 (TPD) is a highly effective species-specific inducer of CYP2Â in rats.... more 2,4,6-Tryphenyldioxane-1,3 (TPD) is a highly effective species-specific inducer of CYP2Â in rats. Several analogs of TPD were synthesized using a reaction with 1,3-diphenylpropane-1,3-diol and corresponding substituted benzaldehydes to verify a hypothesis that minor changes in the inducer structure can cause changes in induction abilities (R=H, cisTPD and transTPD; R=N(CH3)2, pDMA; R=NO2, pNO2; R=F, pF; R=OCH3, pMetO). Male Wistar rats were treated by TPD or its analogs (single injection of 10 mg/kg body weight in corn oil). In rat liver cisTPD and transTPD, pDMA, pNO2, pF administration significantly increased total CYP content (1.3 2.5 fold) and the level of PROD (12 20 fold), CYP2B specific activity, whereas pMetO did not have any effects. Western blot and real-time RT-PCR showed that the increase of PROD in liver is related to the high content of CYP2B proteins and paralleled the increase of CYP2B1 (10 43 fold) and CYP2B2 (8 26 fold) mRNAs. At the same time content of CYP2B prot...