PubMed Health⌕ Search

Biomedical subjects

V N Ivanov

Publications and source records attributed to V N Ivanov.

At least 19 recordsLinked to original sources
PubMed2004

STRA13 interacts with STAT3 and modulates transcription of STAT3-dependent targets.

STRA13 is a pVHL-dependent bHLH transcription factor up-regulated on the mRNA level in multiple cancer cell lines and implicated recently in the regulation of immune cell homeostasis and autoimmunity. In searching for STRA13-interacting proteins with oncogenic potential by the yeast two-hybrid screening, we identified STAT3 beta as a STRA13-binding partner. We showed that STRA13 binds predominantly to phosphorylated (active) STAT3 alpha and beta isoforms via its HLH and C-terminal regions. We also found that STRA13 was able to activate transcription from STAT-dependent cis-elements. Expression of endogenous STRA13 was shown to be cytokine-inducible, consistent with STRA13 involvement in STAT-dependent transcription regulation. We demonstrated that the STAT3-regulated promoter of the pro-apoptotic Fas gene was activated upon STRA13 over-expression and that co-expression of STRA13 with STAT3 beta or STAT3 alpha modulated the transcriptional outcome. Forced expression of STRA13 induced apoptosis, in agreement with the STRA13 activation effect on the Fas promoter. Simultaneous expression of STRA13 and STAT3 beta resulted in alleviation of the STRA13 pro-apoptotic effect. Thus, for the first time, we identify STRA13 as a STAT3 partner and provide a consistent line of evidence for STRA13 involvement into regulation of apoptosis via the STAT pathways.

Amino Acid Sequence↗
PubMed2004

Microbiological monitoring in the biodegradation of sewage sludge and food waste.

AIM: To study the microbiology of intensive, in-vessel biodegradation of a mixture of sewage sludge and vegetable food waste. METHODS AND RESULTS: The biodegradation was performed in a closed reactor with the addition of a starter culture of Bacillus thermoamylovorans SW25 under conditions of controlled aeration, stirring, pH and temperature (60 degrees C). The content of viable bacterial cells, determined by flow cytometry, increased from 5 x 108 g-1 of dry matter to 61 x 108 g-1 for 6 days of the process and then dropped to the initial value at the end of the process. The reductions of organic matter, 16S rRNA of methanogens and coenzyme F420 fluorescence during 10 days of the treatment were 67, 54 and 87% of the initial values, respectively. The biodegradability of the organic matter decreased during the 10 days of the treatment from 3.8 to 1.3 mg CO2 g-1 of organic matter per day. The treatment of sewage sludge and food waste at 60 degrees C did not remove enterobacteria, which are the agents of intestinal infections, from the material. The percentage of viable enterobacterial cells, determined by fluorescent in situ hybridization (FISH) with Enterobacteriaceae-specific oligonucleotide probe and flow cytometry, varied from 1 to 14% of the viable bacterial cells. CONCLUSIONS: The mixture of sewage sludge and food waste can be degraded by the aerobic thermophilic bacteria; the starter culture of Bacillus thermoamylovorans SW25 can be used to perform this process; and enterobacteria can survive under treatment of sewage sludge and food waste at 60 degrees C for 13 days. SIGNIFICANCE AND IMPACT OF THE STUDY: The results show that FISH with an oligonucleotide probe can be used to study not only the growth but also the degradation of biomass. Obtained results could be used to design the bioconversion of sewage sludge and food waste into organic fertilizer.

Bacillus↗
PubMed2001

Expression of ring finger-deleted TRAF2 sensitizes metastatic melanoma cells to apoptosis via up-regulation of p38, TNFalpha and suppression of NF-kappaB activities.

Mechanisms underlying radiation and chemotherapy resistance, the hallmark of human melanoma, are not well understood. Here we demonstrate that expression levels of signal adaptor protein TRAF2 coincide with melanoma resistance to UV-irradiation. Altered TRAF2 signaling by a form of TRAF2, which lacks the ring finger domain (TRAF2DeltaN), increases activities of p38 MAPK, ATF2, and the level of TNFalpha expression. Forced expression of TRAF2DeltaN in HHMSX highly metastatic melanoma cells that lack Fas expression and thus utilize the TNFalpha-TNFR1 as the major apoptotic pathway sensitized cells to UV-induced apoptosis. An over twofold increase in degree of apoptosis was observed in TRAF2DeltaN expressing cells that were treated with actinomycin D, anisomycin or with the radiomimetic drug neocarzinostatin. Sensitization by TRAF2DeltaN is selective since it was not observed in response to either Taxol or cis-platinum treatment. TRAF2DeltaN effects are primarily mediated via p38 since inhibition of p38 reduces, whereas activation of p38 promotes the level of UV-induced apoptosis. Conversely, activation of IKK attenuates the sensitization of melanoma by TRAF2DeltaN, indicating that p38-mediated suppression of NF-kappaB activity is among TRAF2DeltaN effects. Our finding identifies p38, TNFalpha and NF-kappaB among key players that efficiently sensitizes melanoma cells to UV-, ribotoxic (anisomycin) and radiomimetic chemicals-induced programmed cell death in response to aberrant TRAF2 signaling.

Acetyltransferases↗
PubMed2001

Cooperation between STAT3 and c-jun suppresses Fas transcription.

Decreased Fas expression during tumor progression often results in a loss of Fas-ligand (FasL)-mediated apoptosis. Human and mouse melanoma exhibit an inverse correlation between the degree of Fas cell surface expression, tumorigenicity, and metastatic capacity. The expression of dominant negative Stat3 or c-Jun in melanoma cells efficiently increased Fas expression and sensitized cells to FasL-induced apoptosis. Stat3+/- as well as c-Jun-/- cells exhibited increased Fas cell surface expression and higher sensitivity to FasL-mediated apoptosis. Suppression of Fas expression by Stat3 and c-Jun is uncoupled from Stat3-mediated transcriptional activation. Our findings indicate that Stat3 oncogenic activities could also be mediated through its cooperation with c-Jun, resulting in downregulation of Fas surface expression, which is implicated in the tumor's ability to resist therapy and metastasize.

Animals↗
PubMed2001

Jun NH2-terminal kinase phosphorylation of p53 on Thr-81 is important for p53 stabilization and transcriptional activities in response to stress.

The p53 tumor suppressor protein plays a key role in the regulation of stress-mediated growth arrest and apoptosis. Stress-induced phosphorylation of p53 tightly regulates its stability and transcriptional activities. Mass spectrometry analysis of p53 phosphorylated in 293T cells by active Jun NH2-terminal kinase (JNK) identified T81 as the JNK phosphorylation site. JNK phosphorylated p53 at T81 in response to DNA damage and stress-inducing agents, as determined by phospho-specific antibodies to T81. Unlike wild-type p53, in response to JNK stimuli p53 mutated on T81 (T81A) did not exhibit increased expression or concomitant activation of transcriptional activity, growth inhibition, and apoptosis. Forced expression of MKP5, a JNK phosphatase, in JNK kinase-expressing cells decreased T81 phosphorylation while reducing p53 transcriptional activity and p53-mediated apoptosis. Similarly transfection of antisense JNK 1 and -2 decreased T81 phosphorylation in response to UV irradiation. More than 180 human tumors have been reported to contain p53 with mutations within the region that encompasses T81 and the JNK binding site (amino acids 81 to 116). Our studies identify an additional mechanism for the regulation of p53 stability and functional activities in response to stress.

Animals↗
PubMed2001

Transcription factors NF-kappaB and AP-1/c-fos in cell response to nocodazole.

The effects of nocodazole (an agent causing degradation of microtubules in vitro) on the content of transcription factors NF-kappaB and AP-1/c-fos in the nuclei of cultured cells CHO-K1 and HeLa, as well as on the activity of these factors in the nuclei of T-cell hybridoma 2B4 were studied. Immunoblotting, immunofluorescence, and gel retardation techniques revealed that in all cell lines studied nocodazole induced rapid and considerable activation (an increased content in the nuclei) of transcription factor AP-1/c-fos. In 2B4 cells, nocodazole had no effect on the activity of NF-kappaB, but in CHO-K1 and HeLa cells it caused a transient decrease, sometimes followed by an increase in the content of subunit p50. Besides, nocodazole inhibited proteolytic degradation of NF-kappaB in CHO-K1 and HeLa cells and caused a short-term decrease in the content of subunit p65 in CHO-K1 cells. The results suggest that nocodazole may interfere with the genome expression, and these alterations should be taken into consideration, whatever experimental studies this substance is used in.

Animals↗
PubMed2000

Number of triplets in 16S rRNA gene related with pathogenicity of Bacillus spp. and Clostridium spp.

The relation between the number of some trinucleotides in the sequence of 16S rRNA gene and pathogenicity of bacterial species from the genera of Bacillus and Clostridium was revealed. The species of genus Bacillus, which are pathogenic for humans, mammals and insects, have an increased number of AAA and TAT triplets in 16S rRNA gene. Theoretically, these species, B. anthracis and B. cereus for example, may be detected in the specimen by the higher ratio of AAA plus TAT triplets to the number of GGG triplet. Species of genus Clostridium, which are pathogenic for humans and mammals, have a maximum ratio of AAA and TAT triplet numbers. This ratio was higher than 2.6 for pathogenic species and lower than 2.2 for saprophytic ones. These theoretical data may open a new way for detecting pathogenic bacteria through the determination of triplet numbers in the sequences of 16S rRNA or rRNA. However, the mechanism of evolutionary relation between the number of AAA and TAT triplets in the sequence of 16S rRNA gene and the pathogenicity of bacterial species is not known.

Bacillus↗
PubMed2000

Glutathione S-transferase p elicits protection against H2O2-induced cell death via coordinated regulation of stress kinases.

To elucidate mechanisms underlying glutathione S-transferase p (GSTp)-mediated cellular protection against oxidative stress-induced cell death, the effect of GSTp on stress signaling pathways was investigated before and after H2O2 treatment. Under nonstressed conditions, increased expression of GSTp via a tet-off-inducible GSTp in NIH 3T3 cells increased the phosphorylation of mitogen-activated protein (MAP) kinase kinase 4, p38, extracellular receptor kinase (ERK), and inhibitor of kappa-kinase (IKK), and reduced phosphorylation of MAP kinase kinase 7 and Jun NH2-terminal kinase (JNK). Whereas H2O2 treatment of cells induced JNK, p38, and IKK activities, in the presence of H2O2 and elevated GSTp expression there was an additional increase in ERK, p38, and IKK activities and a decrease in JNK activity. GSTp-mediated protection from H2O2-induced death was attenuated upon inhibition of p38, nuclear factor KB, or MAP kinase by dominant negative or pharmacological inhibitors. Conversely, expression of a dominant negative JNK protected cells from H2O2-mediated death. These data suggest that the coordinated regulation of stress kinases by GSTp, as reflected by increased p38, ERK, and nuclear factor kappaB activities together with suppression of JNK signaling, contributes to protection of cells against reactive oxygen species-mediated death.

3T3 Cells↗
PubMed2000

p38 protects human melanoma cells from UV-induced apoptosis through down-regulation of NF-kappaB activity and Fas expression.

Identifying mechanisms that underlie the resistance of human melanoma to radiation and chemotherapy is expected to assist in developing new strategies for the treatment of this tumor type. We recently demonstrated that through up-regulation of TNFalpha, ATF2 increases the resistance of late stage melanoma cells to apoptosis induced by UV-irradiation. In elucidating the role of ATF2 kinases, we now demonstrate that ASK1/MKK6/p38 elicits suppression of Fas expression. ASK1/p38 downregulates the expression of a Fas via NF-kappaB/SP1 site on the Fas promoter. Deletion or mutation of NF-kappaB/SP1 within the Fas promoter abrogates p38 effect. ASK1/p38 silences the Fas promoter by inhibition of IkappaBalpha phosphorylation - thereby limiting NF-kappaB activity. Forced expression of a dominant negative form of p38 (p38-ASP) or treatment with p38 pharmacological inhibitor, SB203580, increases NF-kappaB activity, Fas expression and the levels of UVC-induced apoptosis in late stage melanoma cells. Inhibition of p38 activity also restored NF-kappaB activity and Fas expression in early-phase melanoma cells, suggesting that p38 elicited suppression of Fas expression is not restricted to late phase melanoma. Identifying p38-mediated down-regulation of Fas expression illustrates a novel regulatory pathway by which ASK1/MKK6/p38 alters the degree and nature of the UV-induced apoptosis of melanoma cells. Oncogene (2000).

Apoptosis↗
PubMed2000

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis.

Radiation resistance is a hallmark of human melanoma, and yet mechanisms underlying this resistance are not well understood. We recently established the role of ATF2 in this process, suggesting that stress kinases, which contribute to regulation of ATF2 stability and activity, play an important role in the acquisition of such resistance. Here we demonstrate that changes in the expression and respective activities of TRAF2/GCK occur during melanoma development and regulate its sensitivity to UV-induced apoptosis. Comparing early- and late-stage melanoma cells revealed low expression of TRAF2 and GCK in early-stage melanoma, which coincided with poor resistance to UV-induced, TNF-mediated apoptosis; forced expression of GCK alone or in combination with TRAF2 efficiently increased JNK and NF-kappaB activities, which coincided with increased protection against apoptosis. Conversely, forced expression of the dominant negative form of TRAF2 or GCK in late-stage melanoma cells reduced NF-kappaB activity and decreased Fas expression, resulting in a lower degree of UV-induced, Fas-mediated cell death. Our results illustrate a mechanism in which protection from, or promotion of, UV-induced melanoma cell death depends on the nature of the apoptotic cascade (TNF or Fas) and on the availability of TRAF2/GCK, whose expression increases during melanoma progression. Oncogene (2000) 19, 933 - 942.

Apoptosis↗
PubMed2000

TNF-alpha is the critical mediator of the cyclic AMP-induced apoptosis of CD8+4+ double-positive thymocytes.

Apoptosis is one of the key regulatory mechanisms in tissue modeling and development. In the thymus, 95-98% of all thymocytes die by apoptosis because they failed to express a TCR with an optimal affinity for the selecting intrathymic peptide-MHC complexes. We studied the possible role of two prominent nerve growth factor (NGF-TNF) family member systems, Fas ligand (FasL)-Fas receptor (FasR) and TNF-alpha-TNFR, in apoptosis of murine CD8+4+ double-positive (DP) thymocytes induced via TCR-CD3- and cAMP-mediated signaling. TCR-CD3epsilon-mediated apoptosis of DP thymocytes was found not to be dependent on either of the two systems. The FasL-FasR system was also found to be dispensable for the cAMP-mediated apoptosis. By contrast, cAMP agonists (dibutyryl-cAMP and forskolin) induced apoptosis via TNF-alpha, as evidenced by 1) the ability of anti-TNF-alpha mAbs to abrogate cAMP analogue-induced DP apoptosis in a dose-dependent manner; and 2) increased resistance of DP thymocytes from TNF-alpha-/- and TNFR I-/-II-/- animals to cAMP agonist-mediated apoptosis. cAMP agonists induced DP thymocyte death by a combination of two mechanisms: first, they induced selective up-regulation of TNF-alpha production, and, second, they sensitized DP thymocytes to TNF-alpha. The latter effect may be due to the down-regulation of TNFR-associated factor 2 protein. These results identify TNF-alpha as the critical mediator of cAMP-induced apoptosis in thymocytes and provide a molecular explanation for how the cAMP stimulators, including the sex steroids, may modulate T cell production output, as observed under physiological and pharmacological conditions.

Animals↗
PubMed2000

Sex steroids induce apoptosis of CD8+CD4+ double-positive thymocytes via TNF-alpha.

T cell production by the thymus, thymic size, cellularity and output all decrease drastically after puberty. Among the candidates that may mediate this decrease are the sex steroids: hypersecretion or pharmacological administration of these hormones has long been known to induce thymic hypocellularity, and their depletion yields thymic hypercellularity. Here we show that a typical sex steroid, testosterone, specifically targets CD8+CD4+ double-positive (DP) thymocytes for apoptosis via TNF-alpha. Anti-TNF-alpha monoclonal antibodies abrogated testosterone-induced DP apoptosis, and TNF-alpha-/- DP thymocytes were largely resistant to testosterone-mediated apoptosis in vivo. Testosterone accomplished this effect by upregulating TNF-alpha production and by simultaneously sensitizing DP thymocytes to TNF-alpha. Thus, TNF-alpha is the critical mediator of sex steroid-induced apoptosis in thymocytes, and its manipulation should provide a point of intervention to modulate T cell production in sex hormone disorders.

Animals↗
PubMed2000

Labelled trinucleotides as quantitative probes to identify Bacillus spp. using fluorescent in situ hybridization.

The number of nucleotide triplet repeats in 16 S rRNA sequences can be used for detection and identification of bacteria. Labelled TTT, GGG and ATA triplets were hybridized to the ribonucleic acid of Bacillus subtilis and Bacillus fusiformis whole-cells and the number of such triplets was quantified by synchronous fluorescence spectrometry. Each species was distinctly identified by specific ratios of labelled TTT, GGG and ATA triplets as well as characteristic fluorescence spectra. Notwithstanding the absence of intrinsic specificity, fluorescein-conjugated nucleotide triplet probes appear to be a useful tool for fluorescent spectrometric identification of micro-organisms through the quantitation of trinucleotide repeats.

Bacillus↗
PubMed2000

[The formation and developmental outlook of medical rehabilitation in the Armed Forces of the Russian Federation].

In medical service system of AF RF rehabilitation means combination of medical, military and professional, social and economic and pedagogical measures directed to recovery of health, fighting efficiency (ability to work) which were disturbed or lost by servicemen because of disease or trauma. In the article the main landmarks of rehabilitation development in Russian military medicine are pointed out, today's state of system on the whole and stages in particular is analyzed, perspectives of development are determined. The authors have noted considerable contribution made by Central Military Clinical Hospital N 6 to development of medical rehabilitation. Arsenal of modern rehabilitation and restorative measures is indicated. Methodological principles of rehabilitation conduction are shown. The main ways in further improvement of medical rehabilitation are development of its specialization, rise in economic and social efficiency of rehabilitation measures at the expense of significant unloading of hospital urgent beds and decrease in periods of patient return to military service who will be ready to perform their duties in whole volume. Introduction of modern methodological and organizational principles of medical rehabilitation into the practice of medical support of the Armed Forces' personnel will contribute to achievement of success in this area.

Adult↗
PubMed2000

[Possible mechanisms of development of biliary diseases under the conditions of the Transbaikal region].

Eighty one patients with various biliary diseases and 36 apparently healthy individuals were examined. There were relatively elevated lipid peroxidation (LPO) products (E 232/220 and E 278/220) in biliary diskynesia and higher concentrations of LPO intermediate products in cholecystitis. In cholelithiasis, the levels of LPO products were lower than those in cholecystitis. E 232/220 and 278/220 may be used for early diagnosis of biliary dysfunctions. Selenium deficiency observed in the Transbaikal region decreases antiradical protection and increases the incidence of biliary diseases.

Bile Duct Diseases↗