EFFECTS OF CHROMIUM (VI) ON PROCESS OF LIPID PEROXIDATION AND ANTIOXIDANT SYSTEM IN THE CELLS OF LIVER, KIDNEY AND LUNG OF RABBITS

У статті показані результати досліджень впливу шестивалентного Хрому за умов внутрішньошлункового введення у формі K2Cr2O7 на процес пероксидного окиснення ліпідів (ПОЛ) та активність ензимів антиоксидантної системи (супероксиддисмутаза, каталаза, глутатіонпероксидаза, глутатіонредуктаза) в клітинах печінки, нирки і легень кроликів. Встановлено, що 30-добове введення K2Cr2O7 дозою 5 мг/кг маси зумовлює стимуляцію процесу ПОЛ та неоднозначні зміни активності ензимів-антиоксидантів в органах кроликів. Отримані результати свідчать про різну стійкість аналізованих клітин до зумовленого Хромом(VI) оксидативного стресу та специфіку адаптаційних антиоксидантних реакцій у клітинах внутрішніх органів тварин.В работе представлены результаты исследований влияния шестивалентного хрома в условиях внутрижелудочного введения в форме K2Cr2O7 на процесс перекисного окисления липидов (ПОЛ) и активность ферментов антиоксидантной системы (супероксиддисмутаза, каталаза, глутатионпероксидаза, глутатионредуктаза) в клетках печени, почек и легких кроликов. Установлено, что 30-суточное введение K2Cr2O7 в дозе 5 мг/кг массы приводит к стимуляции процесса ПОЛ и неоднозначным изменениям активности ферментов-антиоксидантов в органах кроликов. Полученные результаты свидетельствуют о различной устойчивости анализируемых клеток к обусловленному хромом(VI) окислительному стрессу и специфике адаптационных антиоксидантных реакций в клетках внутренних органов животных.The aim of this study was to assess an impact of hexavalent chromium in the conditions of intragastric administration in the form of K2Cr2O7 on the process of lipid peroxidation (LPO) and activities of enzymes of antioxidant system (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) in the cells of liver, kidney and lungs of rabbits. It was found that 30-daily administration of K2Cr2O7 at a dose of 5 mg / kg caused stimulation of lipid peroxidation and diverse changes in activity of antioxidant enzymes in the organs of rabbits. The results of study indicate the different resistance of analyzed cells to oxidative stress caused by chromium (VI) and specificity of adaptive antioxidant reactions in the cells of internal organs of animals

БІОМОНІТОРИНГ ЕКОЛОГІЧНОГО СТАНУ ПРИРОДНИХ ВОДОЙМ

The review article analyzes an importance of water bodies monitoring to develop the appropriate measures for improving their environmental condition. It is shown that the use of chemical approaches alone to determine the quality of water as a living environment for aquatic organisms is insufficient for environmental assessment of the components of hydrosphere. It is due to the difficulties of identifying all the diversity of available anthropogenic pollutants of water environment, of assessing their interaction, migration and transformation in water and water body inhabitants. However, biological analysis methods more reflect the relationship between bioavailability of xenobiotics and other contaminants, their content in the cells of aquatic organisms and toxic effect on hydrobionts. These reasons provide the advantages of biomonitoring methods such as bioindication and biological testing, over the methods of chemical analysis of water bodies and watercourses. Application of these methods will greatly help to identify environmental risks, selecting the most promising measures for the successful implementation of water bodies management.  В обзорной статье проанализировано значение мониторинга водных объектов с целью разработки соответствующих мероприятий по улучшению их экологической состояния. Показано, что применение одних химических подходов для определения качества воды как среды обитания водных организмов недостаточно для экологической оценки компонентов гидросферы, учитывая трудности выявления всего разнообразия имеющихся в водной среде антропогенных загрязнителей, оценки их взаимодействия, миграции и трансформации в воде и в организме жителей водоемов. Зато биологические методы анализа в большей степени отражают связь между биодоступностью ксенобиотиков и других загрязнителей, их содержанием в клетках водных организмов и токсическим воздействием на гидробионтов. Это свидетельствует на преимущества использования методов биомониторинга, таких как биоиндикация и биотестирование, над химическими методами анализа водоемов и водотоков. Применение этих методов будет способствовать эффективному выявлению экологического риска, выбора перспективных мероприятий для успешного менеджмента водных объектов.В оглядовій статті проаналізовано значення моніторингу водних об’єктів з метою розробки відповідних заходів щодо його поліпшення їхнього екологічної стану. Показано, що застосування самих лише хімічних підходів для визначення якості води як середовища життя водяних організмів недостатнє для екологічної оцінки компонентів гідросфери з огляду на труднощі виявлення всієї різноманітності наявних у водному середовищі антропогенних полютантів, оцінки їхньої взаємодії, міграції й трансформації у воді та організмі мешканців водойм. Натомість біологічні методи аналізу більшою мірою віддзеркалюють зв’язок між біодоступністю ксенобіотиків та інших забруднювачів, їхнім вмістом у клітинах водяних організмів і токсичним впливом на гідробіонтів. Це зумовлює переваги використання методів біомоніторингу, таких як біоіндикація і біотестування, над хімічними методами аналізу водойм і водотоків. Застосування цих методів сприятиме ефективному виявленню екологічного ризику, вибору перспективних заходів для успішного менеджменту водних об’єктів. &nbsp

Transglutaminase 2 facilitates the distant hematogenous metastasis of breast cancer by modulating interleukin-6 in cancer cells

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Introduction Inflammation has been implicated in cancer aggressiveness. As transglutaminase 2 (TG2), which has been associated with inflammatory signaling, has been suggested to play a role in tumor behavior, we propose that TG2 may be an important linker inducing interleukin (IL)-6-mediated cancer-cell aggressiveness, including distant hematogenous metastasis. Methods To investigate the role for TG2 and IL-6, TG2-knocked-down and IL-6-knocked-down cancer cells were generated by using shRNA. Human breast cancer cell xenograft model in highly immunocompromised mice and human advanced breast cancer primary tumor tissue microarrays were used in this study. Results IL-6 production in human breast cancer cells was dependent on their TG2 expression level. In vitro tumor-sphere formation was dependent on TG2 and downstream IL-6 production from cancer cells. Primary tumor growth in the mammary fat pads and distant hematogenous metastasis into the lung was also dependent on TG2 and downstream IL-6 expression levels. The effect of TG2 expression on human breast cancer distant metastasis was investigated by analyzing a tissue microarray of primary tumors from 412 patients with their clinical data after 7 years. TG2 expression in primary tumor tissue was inversely correlated with recurrence-free survival (P = 0.019) and distant metastasis-free survival (DMFS) (P = 0.006) in patients with advanced breast cancer. Furthermore, by using public datasets that included a total of 684 breast cancer patients, we found that the combined high expression of TG2 and IL-6 was associated with shorter DMFS, compared with the high expression of IL-6 only (P = 0.013). Conclusions We provide evidence that TG2 is an important link in IL-6-mediated tumor aggressiveness, and that TG2 could be an important mediator of distant metastasis, both in a xenograft animal model and in patients with advanced breast cancer

Involvement of JNK-mediated pathway in EGF-mediated protection against paclitaxel-induced apoptosis in SiHa human cervical cancer cells

We investigated the signalling pathways by which epidermal growth factor (EGF) modulates paclitaxel-induced apoptosis in SiHa human cervical cancer cells. SiHa cells exposed to paclitaxel underwent apoptosis, which was strongly inhibited by EGF. This inhibition of apoptosis by EGF was not altered by pharmacological blockade of phosphatidylinositol 3′-OH kinase (PI-3K) with the PI-3K specific inhibitor LY294002 or blockade of the mitogen-activated protein kinase (MAPK) kinase (MEK) with the MEK specific inhibitor PD98059, or by transfection of the cells with PI-3K or MEK dominant-negative expression vectors. EGF did not stimulate PI-3K/Akt, MEK/MAPK, or p38 MAPK activity in SiHa cells but did transiently activate the c-Jun NH2-terminal kinase (JNK). Co-exposure of SiHa cells to SB202190 at concentrations that inhibit JNK abolished the protective effect of EGF on SiHa cells against paclitaxel-induced apoptosis. Our findings indicate that the JNK signaling pathway plays an important role in EGF-mediated protection from paclitaxel-induced apoptosis in SiHa cells. © 2001 Cancer Research Campaign http://www.bjcancer.co

Interplay between transglutaminases and heparan sulphate in progressive renal scarring

Transglutaminase-2 (TG2) is a new anti-fibrotic target for chronic kidney disease, for its role in altering the extracellular homeostatic balance leading to excessive build-up of matrix in kidney. However, there is no confirmation that TG2 is the only transglutaminase involved, neither there are strategies to control its action specifically over that of the conserved family-members. In this study, we have profiled transglutaminase isozymes in the rat subtotal nephrectomy (SNx) model of progressive renal scarring. All transglutaminases increased post-SNx peaking at loss of renal function but TG2 was the predominant enzyme. Upon SNx, extracellular TG2 deposited in the tubulointerstitium and peri-glomerulus via binding to heparan sulphate (HS) chains of proteoglycans and co-associated with syndecan-4. Extracellular TG2 was sufficient to activate transforming growth factor-β1 in tubular epithelial cells, and this process occurred in a HS-dependent way, in keeping with TG2-affinity for HS. Analysis of heparin binding of the main transglutaminases revealed that although the interaction between TG1 and HS is strong, the conformational heparin binding site of TG2 is not conserved, suggesting that TG2 has a unique interaction with HS within the family. Our data provides a rationale for a novel anti-fibrotic strategy specifically targeting the conformation-dependent TG2-epitope interacting with HS

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

Accumulation of heavy metals in gametophytes of the epilithic mosses

Heavy metals are hazardous pollutants in urban atmosphere that are released into the environment mainly as a result of industrial activity and high traffic loads. These substances pose a substantial risk to human health and biota in urban ecosystems. Therefore, environmental monitoring of air pollution with metals by using bioindicator species is of great importance. Bryophytes capable of accumulating heavy metals are widely used as bioindicators of environmental pollution for biomonitoring atmospheric metal deposition. The ability of urban epilithic mosses to accumulate heavy metals has not been studied sufficiently. This invistigation was aimed at studying metal-accumula­ting ability of Rhynchostegium murale and Schistidium apocarpum mosses collected within the city of Lviv (Western Ukraine), as well as exploring the relationship between the level of anthropogenic load and the accumulation of heavy metals in moss gametophytes. Two polluted sites in the southern part of the city and one control site in the territory of Stryisky Park were analyzed. The content of heavy metals, namely Cr, Mn, Ni, Pb, and Zn, in moss samples was determined by the atomic absorption spectrophotometry using an atomic absorption spectrometer C-115PK Selmi. The results were processed using statistical methods. It was demonstrated that different levels of metal accumulate in Rhynchostegium murale and Schistidium apocarpum mosses. Depen­ding on the concentration in moss gametophytes sampled in the city of Lviv, the studied metals can be arranged in the following order: Mn> Zn> Cr> Ni> Pb. However, the content of Mn and Zn in the S. apocarpum moss was found to be considerably higher than in R. murale. The gametophytes of both mosses collected in areas subjected to industrial and transport loads in the southern regions of Lviv city had significantly higher concentration of Pb, and R. murale also had an elevated Mn content compared to moss samples collected in green park area. The results of our study suggest that the rate of accumulation of heavy metals in gametophytes of epilithic mosses reflect the level of atmospheric metal deposition in urban areas exposed to the anthropogenic pressures on the environment

Kinetic properties of adenosine triphosphate sulfurylase of intestinal sulfate-reducing bacteria

The investigation of specific activity of ATP sulfurylase and kinetic properties of the enzyme in cell-free extracts of intestinal bacterial strains Desulfovibrio piger Vib-7 and Desulfomicrobium sp. Rod-9 is presented. The microbiological, biochemical, biophysical and statistical methods were used in the work. The optimal temperature (35 ºC) and pH 8.0-8.5 for enzyme reaction were determined. An analysis of kinetic pro­perties of ATP sulfurylase has been carried out. Initial (instantaneous) reaction velocity (V0), maximum amount of the product of reaction (Pmax), the reaction time (half saturation period, τ) and maximum veloci­ty of the ATP sulfurylase reaction (Vmax) have been defined. Michaelis constants (KmSulfate, KmATP, KmAPS, and KmPyrophosphate­) of the enzyme reaction were demonstrated for both D. piger Vib-7 and Desulfomicrobium sp. Rod-9 intestinal bacterial strains