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Biomedical subjects

V V Lyakhovich

Publications and source records attributed to V V Lyakhovich.

At least 19 recordsLinked to original sources
PubMed2006

Active defense under oxidative stress. The antioxidant responsive element.

This review considers the mechanisms and factors that stimulate transcription of genes regulated by the antioxidant responsive element (ARE). The latter is important for cell defense under conditions of oxidative stress and also for detoxification of electrophilic xenobiotics. There are differences in regulation of intracellular homeostasis involving Nrf2-mediated activation of ARE and other redox-sensitive factors (NF-kappaB and AP-1).

Animals↗
PubMed2005

Rat hepatic CYP1A1 and CYP1A2 induction by menadione.

The effects of menadione on activities and expression of cytochrome P450 (CYP) 1A subfamily (CYP1A) isozymes in rat hepatic tissue were examined. When rats were treated orally with 15 mg/kg menadione for 4 days, the elevation of hepatic CYP1A1/1A2 specific activities in microsomal preparations was detected with approximately 5.4- and 2.5-fold increase over control values for ethoxyresorufin-O-deethylase (EROD, CYP1A1) and methoxyresorufin-O-demethylase (MROD, CYP1A2) activities, respectively. CYP1A1 and CYP1A2 mRNA levels in the liver of menadione-treated rats were approximately 11.8- and 1.8-fold higher than in controls, respectively, whereas the expression of the CYP1A regulatory proteins aryl hydrocarbon-receptor (AhR) and AhR nuclear translocator (Arnt) was not changed at the mRNA level. The result of this study demonstrates that menadione induces CYP1A1/1A2 expression in vivo through either transcriptional activation and/or mRNA stabilization.

Actins↗
PubMed2005

Possible role of P-glycoprotein in cyclophosphamide resistance of transplanted mouse RLS lymphosarcoma.

The causes of different sensitivity of mouse LS lymphosarcoma and its resistant RLS variant to cyclophosphamide were studied. Division of LS and RLS cells stops in the G2/M phase 24 h after cyclophosphamide treatment, but this stop lasts for more than 48 h in LS cells and less than 24 h in RLS cells. DNA fragmentation, a marker of apoptosis, is observed only in LS cells starting from 24 h after cyclophosphamide treatment. LS and RLS strains do not differ by the expression of bcl-2, bcl-6, bax, bad, mdr1a, mdr1b genes and P-glycoprotein protein. The strains differ by transport activity of P-glycoprotein, tested by SYTO 16 substrate release from cells: activity of P-glycoprotein in RLS cells was 2-fold higher than in LS cells. Presumably, the resistance of RLS tumor to cyclophosphamide-induced apoptosis is a result of inhibition of the apoptotic cascade by P-glycoprotein which is functionally more active in these cells than in LS cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Transcriptional activation of cytochrome P450 1A1 with alpha-tocopherol.

Peroral administration of alpha-tocopherol in a daily dose of 150 mg/kg for 1, 4, 8, and 12 days leads to induction of cytochromes P450 1A in male rats. Activity of CYP1A1 and CYP1A2 increased most significantly one day after alpha-tocopherol administration (by 2.6 and 2.7 times, respectively). CYP1A1 was immunohistochemically detected in rat liver microsomes during this period. The content of CYP1A1 mRNA significantly increased in the liver. The amount of CYP1A2 mRNA and regulatory proteins for signal activation of CYP1A1 (AhR and Arnt) remained unchanged after treatment with alpha-tocopherol.

Animals↗
PubMed2004

Activity of cytochrome P450 in children.

The 6beta-hydroxycortisol/cortisol ratio was measured in 52 children aging 1.1-14.0 years. The maximum increment in this ratio occurred in the age interval of 1.1-2.0 years. During this period, the regression coefficients in the linear (r=0.57; p=0.044) and nonlinear logarithmic models (r=0.56; p=0.049) were similar. At the age of 10-14 years, the examined ratio attained 19.17+/-17.79.

Adolescent↗
PubMed2004

MDR1 Gene C1236T and C6+139T polymorphisms in the Russian population: associations with predisposition to lymphoproliferative diseases and drug resistance.

Study of MDR1 polymorphism in intron 6 and exon 12 of healthy individuals and patients with chronic lymphoproliferative diseases showed that the presence of mutant 6+139T allele is a factor determining resistance to lymphoproliferative diseases. Comparison of genotyping results in 53 patients and the data on the efficiency of drug therapy showed no significant associations of C(6+139)T and C(1236)T genotypes with drug resistance.

Adolescent↗
PubMed2004

Dynamics of DNA-protein complex formation in rat liver during induction by phenobarbital and triphenyldioxane.

CYP2B gene expression in liver of rats treated with phenobarbital and triphenyldioxane at early stage of induction (40 min-18 h) was studied using electrophoretic mobility shift assay (EMSA) and RT-PCR. During first 6 h after induction, differences in the dynamics of formation of DNA-protein complexes were shown for each inducer. Later (18 h after induction), the intensity pattern of these complexes became the same for both phenobarbital and triphenyldioxane treated animals. This suggests the existence of specific signaling for each inducer only in early stages of CYP2B activation. Increase in nuclear protein (possible transcription factor) binding to Barbie-box regulatory sequence of CYP2B genes was accompanied by their increased expression. Thus, we have demonstrated for the first time that early stages of induction (40 min and 3 h after administration of phenobarbital and triphenyldioxane, respectively) are accompanied by activation of nuclear proteins that can bind to Barbie-box element of CYP2B. Although various chemical inducers cause distinct activation of such binding, this process involves activation of gene transcription.

Animals↗
PubMed2003

Relationship between glutathione S-transferase P1 polymorphism and bronchial asthma and atopic dermatitis.

We determined the prevalence of GSTP1-Ile105 and GSTP1-Val105 alleles in patients with bronchial asthma and atopic dermatitis and healthy children of 2 groups (randomized and nonatopic control). The GSTP1-Ile105/Val105 genotype determines the resistance to atopic dermatitis (odds ratio=0.51; 95% confidence interval: 0.28-0.92; p=0.023). However, both homozygotes are at high risk of developing atopic dermatitis (near-significant differences).

Alleles↗
PubMed2003

Dose-dependent effect of alpha-tocopherol on activity of xenobiotic metabolizing enzymes in rat liver.

Oral treatment with alpha-tocopherol for 4 days dose-dependently increased the content of cytochrome P450 (CYP), catalytic activities of CYP1A1, CYP1A2, CYP2B1, CYP2C, and activity of NADPH-cytochrome-P450 reductase in the liver of male rats, but did not change activity of glutathione S-transferase. These results suggest that alpha-tocopherol induced the enzymes of phase I of xenobiotic metabolism, including CYP1 and CYP2 families involved in the metabolism of drugs and procarcinogenes.

Animals↗
PubMed2003

Possible prediction of the efficiency of chemotherapy in patients with lymphoproliferative diseases based on MDR1 gene G2677T and C3435T polymorphisms.

Study of polymorphism in MDR1 gene exons 21 and 26 revealed that T2677T and T3435T alleles are not a factor predisposing to lymphoproliferative diseases, but they determine the efficiency chemotherapy. Individuals with T2677T and T3435T haplotypes are at highest risk of drug resistance. Association between genotypes G2677T and C3435T was detected in normal subjects and in patients with lymphoproliferative diseases.

Alleles↗
PubMed2003

Functional activity of P-glycoprotein in lymphocytes of patients with lymphoproliferative diseases.

Functional activity of P-glycoprotein in lymphocytes of patients with lymphoproliferative diseases was studied using rhodamine 123. Functional activity of P-glycoprotein in patients receiving a course of chemotherapy was lower than in controls. P-glycoprotein activity was higher in patients receiving more aggressive therapy. Initially activity of P-glycoprotein was higher in patients who did not respond to chemotherapy in comparison with those whose clinical status improved after a course of chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Induction of the CYP2B genes by triphenyldioxane treatment in the rat liver.

Triphenyldioxane (TPD) is a potent phenobarbital-type (PB) inducer of the CYP2B cytochrome isoforms, the inducing effect of which is one order of magnitude higher than PB. The fact that TPD is unable to induce CYP2B genes having the proximal promoter disrupted (mouse Cyp2b10) suggests an existence of the proximal promoter-dependent mechanism of the CYP2B induction. So a TPD-dependent activation of the nuclear proteins to the binding with Barbie-box sequence (the most conservative part of the proximal promoter) was studied. In the nuclear extracts from the intact rat liver there were detected five proteins that could be activated to the Barbie-box binding by the TPD treatment in vitro (II, III, NI, NII and NIII). The first three were effected also by another PB-like inducers tested (PB and TCPOBOP), when NII and NIII complexes were formed under the influence of TPD only. It is possible that a direct activation of the NII and NIII proteins by TPD exists as (3)H-labeled TPD was detected in the composition of NII and NIII complexes. However, both of them disappeared from the nuclear extracts after the long exposure time with TPD (6 h or more). A short induction by the direct intra-liver delivery of TPD (15-30 min) led to the stabile activation of one TPD-specific protein. Apart from the activation of the Barbie-box-binding protein, the short TPD treatment caused the activation of three nuclear proteins being able to interact with the NR1 sequence of the distal promoter PBREM element. These findings suggest that TPD is really the first member of the PB-like inducers family for which a special mechanism of CYP2B induction may exist.

Animals↗