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Biomedical subjects

Maxim L Filipenko

Publications and source records attributed to Maxim L Filipenko.

5 recordsLinked to original sources

o-Aminoazotoluene does induce the enzymes of its own mutagenic activation in mouse liver.

The objective of this study was to investigate the CYP1A1 and CYP1A2 mRNAs and enzyme activities in mouse liver during induction with o-aminoazotoluene (OAT) as well as the capability of the hepatic S9-fraction from OAT-treated mice to induce its own activation to mutagens in the Ames test using S. typhymurium strain TA98. The data obtained indicate that when used at appropriate doses, OAT is a PAH-type inducer of mouse hepatic microsomal monooxygenases, which activity is not less than that of the known inducer 3,4-benzo[alpha]pyrene. In the absence of S9-fraction enzymes no OAT-mediated mutagenicity was observed in the Ames test. In the presence of the S9-fraction from OAT-pretreated mice, OAT induced as high revertant numbers, as it did in the presence of the S9 fraction from the liver of Aroclor 1254-treated mice. Thus, OAT does induce the enzymes of its own mutagenic activation in mouse liver.

Animals↗

Decrease of kappa-opioid receptor mRNA level in ventral tegmental area of male mice after repeated experience of aggression.

Brain opioid systems have been implicated in the regulation of social interaction, including agonistic behaviour. kappa-Opioid receptor B and C mRNA levels were decreased in the ventral tegmental area but not in the nucleus accumbens in male mice with repeated experience of social victories (winners), but not in mice after social defeats (losers) after 10 but not 20 days of confrontations. mu-Opioid receptor mRNA levels were not changed.

Aggression↗

Cytochrome P4501A1 and 1A2 gene expression in the liver of 3-methylcholanthrene- and o-aminoazotoluene-treated mice: a comparison between PAH-responsive and PAH-nonresponsive strains.

The objective of this study was to investigate cytochrome P4501A1 and 1A2 mRNA, protein, and enzyme activity in the liver of male mice differing in the aryl hydrocarbon receptor (AhR) genotype during treatment with the carcinogenic compounds 3-methylcholanthrene (MC) and o-aminoazotoluene (OAT). The basal levels of the CYP1A1 and CYP1A2 enzyme activities were comparable among the mouse strains examined. Significant interstrain variations were observed after treatment by the inducers: EROD and MROD activities were considerably increased in C57BL and A/Sn mice, but not in AKR, SWR, and DBA mice. Western blot analysis did not detect CYP1A1 in the liver of untreated mice. Treatment of mice with MC or OAT caused CYP1A1 accumulation in the liver of C57BL and A/Sn mice, but not in AKR, SWR, and DBA mice. CYP1A2 was detected in all studied mouse strains in both untreated and inducer-treated livers. The results of multiplex RT-PCR showed that the CYP1A1 mRNA in the liver of untreated mice was hardly detectable while constitutive expression of the CYP1A2 gene was rather high. After treatment with MC and OAT the CYP1A1 mRNA level dramatically increased in all strains examined while the increase in the CYP1A2 mRNA level was not striking. This finding did not correlate with the data on the enzyme activity. Our results demonstrated a discrepancy between the transcription of CYP1A1 and CYP1A2 genes and the inducibility of these enzymes in the liver of mice, suggesting a posttranscriptional mechanism of cytochrome P4501A regulation. This comparison between aromatic hydrocarbon-responsive and -nonresponsive strains could contribute to understanding of cytochrome P4501A gene regulation in the liver under the influence of environmental factors.

Animals↗

Repeated experience of social defeats increases serotonin transporter and monoamine oxidase A mRNA levels in raphe nuclei of male mice.

Serotonin transporter (SERT) and monoamine oxidase A (MAOA) mRNA levels in the raphe nuclei area of the midbrain were measured by the multiplex reverse transcription-polymerase chain reaction method in male mice with repeated experience of social victories (winners) and defeats (losers) in ten daily agonistic confrontations. Experiments revealed enhanced SERT and MAOA mRNA levels in the losers compared with the winners and controls. It has been supposed that SERT and MAOA genes are involved in enhancement of serotonin inactivation in response to the increase of serotonergic activity shown earlier in the losers. A positive correlation between MAOA and SERT mRNA levels in the raphe nuclei area of the midbrain was shown.

Acute Disease↗

Alternative splicing of mRNA of mouse interleukin-4 and interleukin-6.

Interleukin-4 and interleukin-6 are multifunctional regulatory proteins, which participate both in haemopoiesis and in immunopoiesis. The alternative splicing of these interleukins in humans is known to proceed in a tissue-specific manner. Additionally, changes in splicing can also be dependent on tissue pathology. In this work, we report on the presence of alternatively spliced mRNA (IL-4delta2mRNA), lacking exon 2, in mouse bone marrow and spleen cells. We find that in unstimulated cells IL-4mRNA levels strongly dominate over IL-4delta2mRNA levels. Both increase in response to stimulation, with the concentration of the alternative variant rising earlier and faster than that of the full-length variant. In all other tissues studied dominance of IL-4delta2mRNA over the full-length variant was not observed. In addition, we find expression of three forms of IL-6 mRNA: the full-length IL-6 mRNA, IL-6Delta3 mRNA, and IL-6Delta5 mRNA in the second and third trimester placenta tissue and in the spleen of mice immunized with a high dose of sheep erythrocytes. It is anticipated that translation of these mRNA variants can generate proteins capable of binding to some subunits of the IL-6 receptor, thus possessing effector function. Alternative splicing is discussed as a source of cytokines with new regulatory properties.

Alternative Splicing↗