20 research outputs found
Exposure of vanadium as a factor of adverse activation of lymphocytes
We have estimated effect of vanadium influence on apoptosis of peripheral blood lymphocytes among workers. Immunologic assessment have allowed establishing that people working under the conditions of vanadium exposure have significantly increased quantity of annexin-positive cells indicating apoptosis in comparison with a reference group of people. We have identified statistically significant adverse mobilization of lymphocytes in respondents who have been working under conditions of the hazardous industry over 10 years. Therefore, the level and duration of the vanadium exposure influenced by the length of em plopent increase the immune system dysfunction degree.ΠΡΠΎΠ²Π΅Π΄Π΅Π½Π° ΠΎΡΠ΅Π½ΠΊΠ° Π²Π»ΠΈΡΠ½ΠΈΡ Π²Π°Π½Π°Π΄ΠΈΡ Π½Π° ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ Π³ΠΈΠ±Π΅Π»Ρ Π»ΠΈΠΌΡΠΎΡΠΈΡΠΎΠ² ΠΏΠ΅ΡΠΈΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΡΠΎΠ²ΠΈ Ρ ΡΠ°Π±ΠΎΡΠ°ΡΡΠΈΡ
. ΠΡΠ΅Π½ΠΊΠ° ΠΈΠΌΠΌΡΠ½Π½ΠΎΠ³ΠΎ ΡΡΠ°ΡΡΡΠ° ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ»Π° ΡΡΡΠ°Π½ΠΎΠ²ΠΈΡΡ, ΡΡΠΎ Ρ ΡΠ°Π±ΠΎΡΠ°ΡΡΠΈΡ
Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΡΠΊΡΠΏΠΎΠ·ΠΈΡΠΈΠΈ Π²Π°Π½Π°Π΄ΠΈΠ΅ΠΌ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ Π°Π½Π½Π΅ΠΊΡΠΈΠ½-ΠΏΠΎΠ·ΠΈΡΠΈΠ²Π½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ, ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡΠΈΡ
ΠΎΠ± Π°ΠΏΠΎΠΏΡΠΎΠ·Π΅, Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΠΎ ΠΏΠΎΠ²ΡΡΠ°Π΅ΡΡΡ ΠΏΠΎ ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ ΠΊ Π³ΡΡΠΏΠΏΠ΅ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ. ΠΡΡΠ²Π»Π΅Π½Π° ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΠ°Ρ Π½Π΅Π³Π°ΡΠΈΠ²Π½Π°Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ Π»ΠΈΠΌΡΠΎΡΠΈΡΠΎΠ² Ρ ΠΎΠ±ΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ
, ΡΠ΅ΠΉ ΡΡΠ°ΠΆ Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
Π²ΡΠ΅Π΄Π½ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²Π° ΠΏΡΠ΅Π²ΡΡΠ°Π» 10 Π»Π΅Ρ. Π’Π°ΠΊΠΈΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, ΡΡΠΎΠ²Π΅Π½Ρ ΠΈ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΡΠΊΡΠΏΠΎΠ·ΠΈΡΠΈΠΈ Π²Π°Π½Π°Π΄ΠΈΠ΅ΠΌ, ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅ΠΌΠ°Ρ ΡΡΠ°ΠΆΠ΅ΠΌ ΡΠ°Π±ΠΎΡΡ, ΡΡΡΠ³ΡΠ±Π»ΡΠ΅Ρ ΡΡΠ΅ΠΏΠ΅Π½Ρ Π΄ΠΈΡΡΡΠ½ΠΊΡΠΈΠΈ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ
EXPERIMENTAL MODELING OF APOPTOSIS UNDER CONDITIONS OF STABLE STRONTIUM EXPOSURE
Apoptosis is defined as a highly regulated form of programmed cell death with typical morphological and biochemical features. A variety of factors, including heavy metals, may influence the intensity of programmed cell death. The aim of the work was to simulate apoptosis in an in vitrosystem under the conditions of stable strontium exposure. The childrenβs population consuming drinking water with high strontium (Sr2+) content (n = 49) was observed. The level of lymphocyte apoptosis was determined with flow cytometry technique, by means of labeled annexin V-FITC conjugate (AnnV-FITC) and propidium iodide (PI) staining. AnnV-FITC+PI- cells were regarded as early apoptotic forms, whereas late apoptotic and/or necrotic cells were AnnV-FITC+PI+. The isolated leukocytes were incubated with Sr2+ at a concentration of 7.0 mg/l, the maximal permitted concentration (MPC) for water of aqueous objects, for 4 hours at 37 ΒΊC. Expression of CD95 and p53 apoptosis markers was performed by flow cytometry using labeled monoclonal antibodies.In vitroexposure to strontium was associated with significantly decreased expression of apoptosisregulating factors, i.e., membrane marker CD95 and intracellular transcription protein p53, 1.56- and 1.68-fold, respectively. Meanwhile, we revealed a significantly (4.68-fold) decreased amounts of AnnV-FITC+PI--cells, as well as a statistically significant (1.35-fold) increase of the AnnV-FITC+PI+-cells. Moreover, the amounts of AnnV-FITC+ PI--lymphocytes in all samples were below the physiological ranges and control values. The number of samples with higher contents of AnnV-FITC+PI+-lymphocyte exceeding the established standards and control values, was 30.8%. Thus, it has been experimentally proven that strontium, at a concentration corresponding to MPC for water objects may significantly inhibit cell death along apoptotic pathways, with switching to necrotic cell death mechanisms, according to phosphatidylserine contents, as detected by annexin V binding test. The data have revealed an ability of strontium to have a significant effect upon the parameters of regulation and maintenance of cellular homeostasis, by influencing the apoptosis intensity, due to shifting a balance towards necrosis and reducing expression of apoptosis-regulating factors. The results of this study may be used in order to identify some marker indexes of immune disorders potentially induced by external influence of strontium upon human health under specific environmental factors
Hydroxylated aromatic hydrocarbons and the cytokine regulation of apoptosis
Organic compounds, at concentrations exceeding their reference ranges, may influence the production of physiological regulators of the cell cycle. The aim of the study was to assess the influence of hydroxylated aromatic hydrocarbons on the cytokine regulation of apoptosis in insulation workers of a chemical enterprise. The organic compounds (phenol, o-cresol, m-cresol, p-cresol) were determined in biological media using capillary gas chromatography. The mediators of intercellular immune regulation - cytokine profile markers (IL6, TNFa, INFy) - were identified by ELISA testing, the level of TNFRI expression was measured using cytofluorometry analysis. The assessment of the cytokine status shows that the examined workers, when exposed to high levels of phenol-containing compounds, demonstrated a credible decrease in the production of the proapoptotic mediators of cellular regulation (TNFa, IFNy) (p<0.05) and a statistically significant reduction in TNFRI expression on lymphocytes (p<0.05). The findings prove the contribution of phenols in the modification of the cytokine status in the workers. Taking into account the specific aromatic hydrocarbons influence on the expression of the physiological regulators of the cell cycle, the impact of phenols may cause immune dysfunction in chemical enterprise workers.ΠΡΠ³Π°Π½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ Π² ΠΏΡΠ΅Π²ΡΡΠ°ΡΡΠΈΡ
ΡΠ΅ΡΠ΅ΡΠ΅Π½ΡΠ½ΡΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ
ΠΌΠΎΠ³ΡΡ ΠΌΠΎΠ΄ΡΠ»ΠΈΡΠΎΠ²Π°ΡΡ ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΡ ΡΠΈΠ·ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠΎΠ² ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Π°. Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ - ΠΎΡΠ΅Π½ΠΈΡΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π°ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ³Π»Π΅Π²ΠΎΠ΄ΠΎΡΠΎΠ΄ΠΎΠ² Π½Π° ΡΠΈΡΠΎΠΊΠΈΠ½ΠΎΠ²ΡΡ ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ Π°ΠΏΠΎΠΏΡΠΎΠ·Π° Ρ ΠΈΠ·ΠΎΠ»ΠΈΡΠΎΠ²ΡΠΈΠΊΠΎΠ² Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²Π°. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΎΡΠ³Π°Π½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ (ΡΠ΅Π½ΠΎΠ», ΠΎ-ΠΊΡΠ΅Π·ΠΎΠ», ΠΌ-ΠΊΡΠ΅Π·ΠΎΠ», ΠΏ-ΠΊΡΠ΅Π·ΠΎΠ») Π² Π±ΠΈΠΎΡΡΠ΅Π΄Π°Ρ
Π²ΡΠΏΠΎΠ»Π½ΡΠ»ΠΎΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΊΠ°ΠΏΠΈΠ»Π»ΡΡΠ½ΠΎΠΉ Π³Π°Π·ΠΎΠ²ΠΎΠΉ Ρ
ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΠΈ. ΠΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΠΌΠ΅Π΄ΠΈΠ°ΡΠΎΡΠΎΠ² ΠΌΠ΅ΠΆΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠΉ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ - ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΡΠΈΡΠΎΠΊΠΈΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΠΏΡΠΎΡΠΈΠ»Ρ (IL6, TNFa, INFy) ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΈΠΌΠΌΡΠ½ΠΎΡΠ΅ΡΠΌΠ΅Π½ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π°, Π΄Π»Ρ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΡΡΠΎΠ²Π½Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° TNFRI ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π»ΠΈ ΡΠΈΡΠΎΡΠ»ΡΠΎΡΠΈΠΌΠ΅ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΌΠ΅ΡΠΎΠ΄. ΠΡΠ΅Π½ΠΊΠ° ΡΠΈΡΠΎΠΊΠΈΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΡΡΠ°ΡΡΡΠ° Π·Π°ΡΠΈΠΊΡΠΈΡΠΎΠ²Π°Π»Π°, ΡΡΠΎ Ρ ΠΎΠ±ΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ
ΡΠ°Π±ΠΎΡΠ°ΡΡΠΈΡ
Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΠΏΠΎΠ²ΡΡΠ΅Π½Π½ΠΎΠΉ ΡΠΊΡΠΏΠΎΠ·ΠΈΡΠΈΠΈ ΡΠ΅Π½ΠΎΠ»ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΠΎ ΡΠ½ΠΈΠΆΠ΅Π½Π° ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΡ ΠΏΡΠΎΠ°ΠΏΠΎΠΏΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΌΠ΅Π΄ΠΈΠ°ΡΠΎΡΠΎΠ² ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ (TNFa, IFNy) (Ρ<0,05) ΠΈ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΠΎ ΠΏΠΎΠ½ΠΈΠΆΠ΅Π½Π° ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΊ ΡΠ°ΠΊΡΠΎΡΡ Π½Π΅ΠΊΡΠΎΠ·Π° ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ Π½Π° Π»ΠΈΠΌΡΠΎΡΠΈΡΠ°Ρ
(Ρ<0,05). Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π°ΡΡ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΠΉ Π²ΠΊΠ»Π°Π΄ ΡΠ΅Π½ΠΎΠ»ΠΎΠ² Π² ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΡΠΈΡΠΎΠΊΠΈΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΡΡΠ°ΡΡΡΠ° ΡΠ°Π±ΠΎΡΠ°ΡΡΠΈΡ
. Π£ΡΠΈΡΡΠ²Π°Ρ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π°ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ³Π»Π΅Π²ΠΎΠ΄ΠΎΡΠΎΠ΄ΠΎΠ² Π½Π° ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΠΈΠ·ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠΎΠ² ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Π°, Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΡΠ΅Π½ΠΎΠ»ΠΎΠ² ΠΌΠΎΠΆΠ΅Ρ ΡΡΠ°ΡΡ ΠΏΡΡΠΊΠΎΠ²ΡΠΌ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠΌ Π΄ΠΈΡΡΡΠ½ΠΊΡΠΈΠΈ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²Π°
Water/Alkali-Catalyzed Reactions of Azides with 2-Cyanothioacetamides. Eco-Friendly Synthesis of Monocyclic and Bicyclic 1,2,3-Thiadiazole-4-carbimidamides and 5-Amino-1,2,3-triazole-4-carbothioamides
The reactions of thioamides with azides in water were studied. It was reliably shown that the reaction of 2-cyanothioacetamides 1 with various types of azides 2 in water in the presence of alkali presents an efficient, general, one-step, atom-economic, and eco-friendly method for the synthesis of 1,2,3-thiadiazol-4-carbimidamides 5 and 1,2,3-triazole-4-carbothioamides 4. This method can be extended to the one-pot reaction of sulfonyl chlorides and 6-chloropyrimidines 2β²o with sodium azide, leading to final products in higher yields, that is, avoiding the isolation of unsafe sulfonyl azides. The method was furthermore applied to the reaction of N,Nβ²-bis-(2-cyanothiocarbonyl)pyrazine 1h with sulfonyl azides to afford bicyclic 1,2,3-thiadiazoles 8 and 1,2,3-triazoles 9 connected via a 1,1β²-piperazinyl linker. 2-Cyanothioacetamides 1 were also shown to react with aromatic azides in water in the presence of alkali to afford 1-aryl-5-amino-1,2,3-triazole-4-carbothioamides 11. In contrast to aromatic azides and similarly to sulfonyl azides, 6-azidopyrimidine-2,4-diones 2o-q react with cyanothioacetamides to form N-pyrimidin-6-yl-5-dialkylamino-1,2,3-thiadiazole-4-N-l-carbimidamides 12. A mechanism was proposed to rationalize the role of water in changing the reactivity of azides toward 2-cyanothioacetamides. Copyright Β© 2019 American Chemical Society.We gratefully acknowledge financial support of this work by the Russian Science Foundation (18-13-00161)
CHIP-mediated degradation and DNA damage-dependent stabilization regulate base excision repair proteins.
Base excision repair (BER) is the major pathway for processing of simple lesions in DNA, including single-strand breaks, base damage, and base loss. The scaffold protein XRCC1, DNA polymerase beta, and DNA ligase IIIalpha play pivotal roles in BER. Although all these enzymes are essential for development, their cellular levels must be tightly regulated because increased amounts of BER enzymes lead to elevated mutagenesis and genetic instability and are frequently found in cancer cells. Here we report that BER enzyme levels are linked to and controlled by the level of DNA lesions. We demonstrate that stability of BER enzymes increases after formation of a repair complex on damaged DNA and that proteins not involved in a repair complex are ubiquitylated by the E3 ubiquitin ligase CHIP and subsequently rapidly degraded. These data identify a molecular mechanism controlling cellular levels of BER enzymes and correspondingly the efficiency and capacity of BER
Overexpression of DNA polymerase Β results in an increased rate of frameshift mutations during base excision repair
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Exchangeability of mammalian DNA ligases between base excision repair pathways
In mammalian cells, DNA ligase IIIalpha and DNA ligase I participate in the short- and long-patch base excision repair pathways, respectively. Using an in vitro repair assay employing DNA ligase-depleted cell extracts and DNA substrates containing a single lesion repaired either through short-patch (regular abasic site) or long-patch (reduced abasic site) base excision repair pathways, we addressed the question whether DNA ligases are specific to each pathway or if they are exchangeable. We find that immunodepletion of DNA ligase I did not affect the short-patch repair pathway but blocked long-patch repair, suggesting that DNA ligase IIIa is not able to substitute DNA ligase I during long-patch repair. In contrast, immunodepletion of DNA ligase IIIa did not significantly affect either pathway. Moreover, repair of normal abasic sites in wild-type and X-ray cross-complementing gene 1 (XRCC1)-DNA ligase IIIalpha-immunodepleted cell extracts involved similar proportions of short- and long-patch repair events. This suggests that DNA ligase I was able to efficiently substitute the XRCC1-DNA ligase IIIa complex during short-patch repair