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General Physiology and Biophysics


Volume 36, 2017, No. 4

Content:


 
Functional and structural characterisation of 5 missense mutations of the phenylalanine hydroxylase.
Martina Pecimonova 1), Emil Polak, Frantisek Csicsay, Kamila Reblova, Maja Stojiljkovic, Zdenko Levarski, Ludovit Skultety, Ludevit Kadasi, Andrea Soltysova

1)Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia. soltysova@fns.uniba.sk.

Phenylketonuria (PKU) and hyperphenylalaninemia (HPA) are a group of genetic disorders predominantly caused by mutations in the phenylalanine hydroxylase (PAH) gene. To date, more than 950 variants have been identified, however the pathogenic mechanism of many variants remains unknown. In this study, in silico prediction and in vitro prokaryotic and eukaryotic expression systems were used to functionally characterize five PAH missense variants (p.F233I, p.R270I, p.F331S, p.S350Y, and p.L358F) previously identified in Slovak and Czech patients. p.F233I, p.R270I, and p.S350Y were classified as deleterious mutations since they showed no specific activity in functional assay and no response to chaperone co-expression. Protein levels of these PAH variants were very low when expressed in HepG2 cells, and only p.S350Y responded to BH4 precursor overload by significant increase in PAH monomer, probably due to reduced rate of protein degradation as the result of proper protein folding. Variants p.F331S and p.L358F exerted residual enzymatic activity in vitro. While the first can be classified as probably pathogenic due to its very low protein levels in HepG2 cells, the latter is considered to be mild mutation with protein levels of approximately 17.85% compared to wt PAH. Our findings contribute to better understanding of structure and function of PAH mutated enzymes and optimal treatment of PKU patients carrying these mutations using BH4 supplementation.

How to cite (APA format):
Pecimonova, M, Polak, E, Csicsay, F, Reblova, K, Stojiljkovic, M, Levarski, Z, Skultety, L, Kadasi, L, Soltysova, A. (2017). Functional and structural characterisation of 5 missense mutations of the phenylalanine hydroxylase. General Physiology and Biophysics, 36(4), 361-371.


 
Biodegradable nanoparticles loaded with tetrameric melittin: preparation and membrane disruption evaluation.
Azucena Gonzalez-Horta 1), Arely Matamoros-Acosta, Abelardo Chavez-Montes, Rocio Castro-Rios, Jorge Lara-Arias

1)Laboratory of Genomic Science, Faculty of Biological Sciences, Universidad Autonoma de Nuevo Leon, 66451 San Nicolas de los Garza, N.L. Mexico. azucena.gonzalezhr@uanl.edu.mx

Melittin is the main component of bee venom consisting of 26 amino acids that has multiple effects, including antibacterial, antiviral and anti-inflammatory in various cell types. This peptide forms pores in biological membranes and triggers cell death. Therefore it has potential as an anti-cancer therapy. However, the therapeutic application of melittin is limited due to its main side effect, hemolysis, which is especially pronounced following intravenous administration. In the present study, we formulated tetrameric melittin-carrying poly-D,L-lactic-co-glycolic acid nanoparticles (PLGA-NPs) and analyzed the lytic activity of this system on liposomes that resembles breast cancer cells. Tetrameric melittin binds avidly to PLGA-NPs with an encapsulation efficiency of 97% and retains its lytic activity demonstrating the effectiveness of PLGA-NPs as nanocarriers for this cytolytic peptide.

How to cite (APA format):
Gonzalez-Horta, A, Matamoros-Acosta, A, Chavez-Montes, A, Castro-Rios, R, Lara-Arias, J. (2017). Biodegradable nanoparticles loaded with tetrameric melittin: preparation and membrane disruption evaluation. General Physiology and Biophysics, 36(4), 373-381.


 
Cross-reacting material 197 (CRM197) affects actin cytoskeleton of endothelial cells.
Bilge Özerman Edis 1), Başak Varol, Ebru Hacıosmanoğlu, Ayhan Ünlü, Muhammet Bektaş

1)Department of Biophysics, Istanbul Faculty of Medicine, Istanbul University, 34390 Çapa, Istanbul, Turkey. bilge.edis@istanbul.edu.tr.

CRM197, cross-reacting material 197, is a mutant of diphtheria toxin (DTx). CRM197 is used in pharmacology as a carrier protein. It has been recently shown that CRM197 causes breakdown in actin filaments. In order to show intracellular localization of CRM197 and visualize cell structure via actin cytoskeleton, endothelial cells were cultured and subjected to CRM197 in vitro. To address the interaction between CRM197 and actin both experimental and theoretical studies were carried out. Colocalization of CRM197 with actin filaments was determined by immunofluorescence microscopy. Following 24-hour incubation, the loss of cell-cell contact between cells was prominent. CRM197 was shown to bind to G-actin by gel filtration chromatography, and this binding was confirmed by Western blot analysis of eluted samples obtained following chromatography. Based on crystal structure, docked model of CRM197-actin complex was generated. Molecular dynamics simulation revealed that Lys42, Cys218, Cys233 of CRM197 interacts with Gly197, Arg62 and Ser60 of G-actin, respectively. CRM197 binding to G-actin, colocalization of CRM197 with actin filament, and actin cytoskeleton rearrangement resulting in the loss of cell-cell contact show that actin comes into sight as target molecule for CRM197.

How to cite (APA format):
Özerman Edis, B, Varol, B, Hacıosmanoğlu, E, Ünlü, A, Bektaş, M. (2017). Cross-reacting material 197 (CRM197) affects actin cytoskeleton of endothelial cells. General Physiology and Biophysics, 36(4), 383-389.


 
Effect of maternal renin-angiotensin-aldosterone system activation on social coping strategies and gene expression of oxytocin and vasopressin in the brain of rat offspring in adulthood.
Tomáš Senko 1), Pavel Svitok, Lucia Kršková

1)Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University in Bratislava, Slovakia. senko5@uniba.sk.

The intrauterine condition in which the mammalian foetus develops has an important role in prenatal programming. The aim of this study was to determine the extent to which activation of the maternal renin-angiotensin-aldosterone system (RAAS) could influence social behaviour strategies in offspring via changes in social neurotransmitters in the brain. Pregnant female Wistar rats were implanted with osmotic minipumps which continually released angiotensin II for 14 days at concentration of 2 μg/kg/h. The adult offspring (angiotensin and control groups) underwent a social interaction test. The mRNA expression of vasopressin, oxytocin and the oxytocin receptor in selected brain areas was measured by in situ hybridisation. Prenatal exposure to higher levels of angiotensin II resulted in a strong trend toward decreased total social interaction time and significantly decreased time spent in close proximity and frequency of mutual sniffing. The angiotensin group showed no changes in oxytocin mRNA expression in the hypothalamic paraventricular or supraoptic nuclei, but this group had reduced vasopressin mRNA expression in the same areas. We concluded that maternal activation of RAAS (via higher levels of angiotensin II) caused inhibition of some socio-cohesive indicators and decreased vasopressinergic activity of offspring. Taken together, these results suggest a reactive rather than proactive social coping strategy.

How to cite (APA format):
Senko, T, Svitok, P, Kršková, L. (2017). Effect of maternal renin-angiotensin-aldosterone system activation on social coping strategies and gene expression of oxytocin and vasopressin in the brain of rat offspring in adulthood. General Physiology and Biophysics, 36(4), 391-398.


 
Obesity- and age-related alterations in FAT/CD36 translocation and lipin-1 subcellular localization in skeletal muscle of the Zucker rats.
Snjezana Romic 1), Katarina Krskova, Rafal Olszanecki, Lucia Balazova, Viktoria Lory, Goran Koricanac, Miroslava Slamkova, Štefan Zórad

1)Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. snjezana.romic@vin.bg.ac.rs.

Fatty acid (FA) uptake and/or intramuscular triglyceride (TG) accumulation in skeletal muscle are increased in obesity, type 2 diabetes and aging. FA translocase (FAT/CD36) translocation, lipin-1 subcellular localization and nuclear factor kappa B (NF-κB) p65 protein content in quadriceps muscle of young and old obese Zucker fa/fa rats and their lean controls were analyzed by immunoblot to define obesity- and aging-related alterations in FA uptake, their subsequent metabolic fate and potential to activate pro-inflammatory signaling. As expected, obesity increased FAT/CD36 content in plasma membrane in quadriceps muscle of fa/fa rats. Aging increased cytosolic lipin-1 content in both, obese rats and their lean controls. Also, old obese rats had decreased level of nuclear extract lipin-1compared to that in old lean rats. Neither obesity nor age altered NF-κB p65 protein content in cytosol and nuclear extract of quadriceps muscle suggesting that obesity/aging-induced changes in FA handling are not accompanied by NF-κB-mediated inflammation. Increase in plasma membrane FAT/CD36 content in obese rats and failure in lipin-1 export to nucleus with progression of obesity, implying an increase in FA uptake and their different channeling into lipid intermediates synthesis pathway in old fa/fa rats versus FA usage in lean rats of the same age.

How to cite (APA format):
Romic, S, Krskova, K, Olszanecki, R, Balazova, L, Lory, V, Koricanac, G, Slamkova, M, Zórad, Š. (2017). Obesity- and age-related alterations in FAT/CD36 translocation and lipin-1 subcellular localization in skeletal muscle of the Zucker rats. General Physiology and Biophysics, 36(4), 399-406.


 
In vitro non-thermal oxidative stress response after 1800 MHz radiofrequency radiation.
Ana Marija Marjanovic Cermak 1), Ivan Pavicic, Blanka Tariba Lovakovic, Alica Pizent, Ivancica Trosic

1)Radiation Dosimetry and Radiobiology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000 Zagreb, Croatia. amarjanovic@imi.hr.

In this study possible connection between radiofrequency exposure (RF) and development of oxidative stress was investigated by measuring impairment in cellular oxidation-reduction balance immediately after RF exposure. Fibroblast cells V79 were exposed for 10, 30 and 60 minutes to 1800 MHz RF radiation. Electric field strength was 30 V/m and specific absorption rate (SAR) was calculated to be 1.6 W/kg. Electromagnetic field was generated within Gigahertz Transversal Electromagnetic Mode cell (GTEM) equipped by signal generator, amplifier and modulator. Cell viability was determined by CCK-8 colorimetric assay and level of reactive oxygen species (ROS) was detected by dihydroethidium staining. Reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) were used to assess cell antioxidant activity while lipid oxidative damage was evaluated measuring concentration of malondialdehyde. Viability of V79 cells remained within normal physiological values regardless of exposure time. Increased level of superoxide radicals was detected after 60-min exposure. Significantly higher GSH level was observed immediately after 10-min exposure with higher but insignificant activity of GSH-Px. Lipid oxidative damage in exposed cell samples was not observed. Short-term RF exposure revealed transient oxidation-reduction imbalance in fibroblast cells following adaptation to applied experimental conditions.

How to cite (APA format):
Marjanovic Cermak, A, Pavicic, I, Tariba Lovakovic, B, Pizent, A, Trosic, I. (2017). In vitro non-thermal oxidative stress response after 1800 MHz radiofrequency radiation. General Physiology and Biophysics, 36(4), 407-414.


 
Effects of extremely low frequency electromagnetic fields on morphine analgesia and tolerance in rats.
Ercan Ozdemir 1), Ayse Demirkazik, Sinan Gursoy, Ahmet Taskıran, Olca Kilinc, Gokhan Arslan

1)Departments of Physiology, School of Medicine, Cumhuriyet University, Sivas, Turkey. ercan_ozdemir@hotmail.com.

Several studies have demonstrated that the electromagnetic fields produce analgesic activity. The aim of this study was to investigate the effects of extremely low frequency (ELF) electromagnetic fields (EMF) on morphine analgesia and tolerance in rats. In the study, 78 adult male Wistar albino rats (approximately 240 ± 12 g) were used. The application of 50 Hz magnetic field, each day the same times for 30 minutes for 15 days, and a total of four times every 15 minute intervals. To constitute morphine tolerance, high dose of morphine (50 mg/kg) were administered for 3 days in rats and tolerance was evaluated on day 4. Prior to analgesia tests, the effective dose (5 mg/kg) of morphine was injected into rats. In the statistical analyzes of the data, analysis of variance (two-way ANOVA) was used and the multiple comparison determined by Tukey tests. The maximum analgesic effect of the 5 mT magnetic field was determined on 7 days. Administration of morphine (5 mg/kg) in rats exposed to a magnetic field, the analgesic effect was significantly higher compared to the morphine group (p < 0.05). Morphine tolerant animals exposed to a magnetic field, the analgesic effect was found significantly higher than morphine tolerant group rats (p < 0.05). Analgesia test data demonstrated that application of ELF-EMFs to rats increases the morphine analgesia and reduces morphine tolerance.

How to cite (APA format):
Ozdemir, E, Demirkazik, A, Gursoy, S, Taskıran, A, Kilinc, O, Arslan, G. (2017). Effects of extremely low frequency electromagnetic fields on morphine analgesia and tolerance in rats. General Physiology and Biophysics, 36(4), 415-422.


 
Research on the effect of formononetin on photodynamic therapy in K562 cells.
Dan Sun 1), Yao Lu, Su-juan Zhang, Kai-ge Wang, Zhe Sun

1)National Center for International Research of Photoelectric Technology and Nano-functional Materials, State Key Laboratory of Cultivation Base for Photoelectric Technology and Functional Materials, Key Laboratory of Optoelectronic Technology of Shaanxi Province, Institute of Photonics and Photo-Technology Northwest University, Xi’an, 710069, China. sund@n.

At the present time, many cancer patients combine some forms of complementary and alternative medicine therapies with their conventional therapies. The most common choice of these therapies is the use of antioxidants. Formononetin is presented in different foods. It has a variety of biological activities including antioxidant and anti-cancer properties. On account of its antioxidant activity, formononetin might protect cancer cells from free radical damage in photodynamic therapy (PDT) during which reactive oxygen species (ROS) production was stimulated leading to irreversible tumor cell injury. In this study, the influence of formononetin on K562 cells in PDT was demonstrated. The results showed that formononetin supplementation alone did not affect the lipid peroxidation, DNA damage and apoptosis in K562 cells. It increases the lipid peroxidation, DNA damage and apoptosis in K562 cells induced by PDT. The singlet oxygen quencher sodium azide suppresses the apoptosis induced by PDT with formononetin. In conclusion, formononetin consumption during PDT increases the effectiveness of cancer therapy on malignant cells. The effect of antioxidants on PDT maybe was determined by its sensitization ability to singlet oxygen.

How to cite (APA format):
Sun, D, Lu, Y, Zhang, S, Wang, K, Sun, Z. (2017). Research on the effect of formononetin on photodynamic therapy in K562 cells. General Physiology and Biophysics, 36(4), 423-430.


 
Purinergic regulation of brain catecholamine neurotransmission: In vivo electrophysiology and microdialysis study in rats.
Eliyahu Dremencov 1), Ľubica Lacinová, Gunnar Flik, Joost Folgering, Thomas Cremers, Ben Westerink

1)Institute of Molecular Physiology and Genetics, Centre for Biosciences, Slovak Academy of Sciences, Bratislava, Slovakia. Eliyahu.Dremencov@savba.sk.

It was previously reported that adenosine-2A (A2A) receptors interact with dopamine-2 (D2) receptors on a molecular level. The aim of the current study was to investigate the functional output of this interaction. In vivo microdialysis was used to assess the effects of an antagonist of A2A receptors, ZM 241385, and an antagonist of D2 receptors haloperidol, either alone or in combination, on brain catecholamine levels. It was found that ZM 241385 did not alter catecholamine levels by its own, but potentiated haloperidol-induced dopamine and norepinephrine release in the nucleus accumbens and prefrontal cortex, respectively. In vivo electrophysiology was used to assess the effect of an agonist (CGS 216820) and an antagonist (ZM 241385) of A2A receptors on the excitability of dopamine and norepinephrine neurons. It was found that CGS 216820 dose-dependently inhibited dopamine and norepinephrine neurons and ZM 241385 reversed this inhibition. In conclusion, those A2A receptors modulate brain catecholamine transmission, and this modulation is mediated, at least in part, via the regulation of excitability of norepinephrine and dopamine neurons. The ability of antagonists of A2A receptors to potentiate the effect of haloperidol on brain norepinephrine and dopamine levels may enhance its clinical efficacy as an antipsychotic drug.

How to cite (APA format):
Dremencov, E, Lacinová, Ľ, Flik, G, Folgering, J, Cremers, T, Westerink, B. (2017). Purinergic regulation of brain catecholamine neurotransmission: In vivo electrophysiology and microdialysis study in rats. General Physiology and Biophysics, 36(4), 431-441.


 
MPP1 interacts with DOPC/SM/Cholesterol in an artificial membrane system using Langmuir-Blodgett monolayer.
Mohamed Elderdfi 1), Jolanta Zegarlińska, Walis Jones, Aleksander Sikorski

1)Department of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, 50-383 Wrocław, Poland. aleksander.sikorski@uwr.edu.pl.

The interaction between membrane palmitoylated protein -1 (MPP1) with lipid bi- and mono-layers composed of a DOPC/SM/Chol mixture was investigated. MPP1 co-migrates with liposomes to the top of the liposome flotation gradient, indicating binding of MPP1 with liposomes. The injection of MPP1 into the subphase of an LB monolayer of the above lipid composition induced an increase in surface pressure, indicating that MPP1 molecules were incorporated into the lipid monolayer. The compressibility modulus isotherms of MPP1, lipids and lipid-MPP1 films have essentially different shapes from one another. Pure MPP1 isotherms were characterized by a peak in surface pressure of 25-35 mNm−1. This transition disappears in isotherms obtained with lipid monolayers in the presence of MPP1, which suggests an interaction between the protein and the lipid monolayers. In addition, this interaction is sensitive to the presence of cholesterol in the lipid monolayer, as adding of MPP1 into the subphase of lipid monolayers containing cholesterol resulted in a much larger increase in surface area than when MPP1 is injected into the subphase of a lipid monolayer devoid of cholesterol. In conclusion, the data demonstrates that MPP1 interacts with lipid mixtures in two different model membrane systems.

How to cite (APA format):
Elderdfi, M, Zegarlińska, J, Jones, W, Sikorski, A. (2017). MPP1 interacts with DOPC/SM/Cholesterol in an artificial membrane system using Langmuir-Blodgett monolayer. General Physiology and Biophysics, 36(4), 443-454.


 
The role of microsomal oxidation in the regulation of monoamine oxidase activity in the brain and liver of rats.
Denis Kozochkin 1), Eugenia Manukhina, H. Fred Downey, Olga Tseilikman, Maria Komelkova, Maria Vasilyeva, Maxim Lapshin, Marat Sahabutdinov, Svetlana Lazuko, Vadim Tseilikman

1)South Ural State University Biomedical School, Chelyabinsk, Russia. vadimed@yandex.ru.

It has been shown in our previous study that monoamine oxidase (MAO) activity in different brain regions are correlated with a microsomal oxidation phenotype. The data obtained in this study, using the microsomal oxidation inhibitor SKF525, and using animals with different duration of hexobarbital sleep, has shown that increased intensity of microsomal oxidation might be associated with increased MAO activity. Since the rats with short hexobarbital sleep time had higher content of hepatic microsomal cytochrome P450 than did rats with long hexobarbital sleep time. In addition, the rats with higher hepatic content of CYP450 had higher activities of MAO-A and MAO-B. Moreover, the microsomal oxidation inhibitor SKF-525 reduced brain and liver activities of MAOA and MAO-B. Consequently, MAO activities in a brain and a liver depend on the microsomal oxidation process.

How to cite (APA format):
Kozochkin, D, Manukhina, E, Downey, H, Tseilikman, O, Komelkova, M, Vasilyeva, M, Lapshin, M, Sahabutdinov, M, Lazuko, S, Tseilikman, V. (2017). The role of microsomal oxidation in the regulation of monoamine oxidase activity in the brain and liver of rats. General Physiology and Biophysics, 36(4), 455-464.


 
Effect of lipoic acid on paraoxonase-1 and paraoxonase-3 protein levels, mRNA expression and arylesterase activity in liver hepatoma cells.
Eray Ozgun 1), Gulben Sayilan Ozgun, Kiymet Tabakcioglu, Selma Suer Gokmen, Necdet Sut, Sevgi Eskiocak

1)Department of Medical Biochemistry, Trakya University School of Medicine, 22030 Edirne. Turkey.drozgune@hotmail.com

Paraoxonase-1 (PON1) and PON3 (PON3) are anti-atherosclerotic enzymes, synthesized primarily in liver and bound to HDL in circulation. The aim of the present study was to investigate the effects of therapeutic doses of lipoic acid on PON1 and PON3 protein levels, mRNA expression and arylesterase activity in liver. We treated HepG2 cells with 10, 40 and 200 μM lipoic acid for 72 h. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. PON1 and PON3 protein levels were measured by Western blotting, their mRNA expression was measured by quantitative PCR and arylesterase activity was measured spectrophotometrically. 200 µM lipoic acid caused a significant increase on PON1 and PON3 protein levels and arylesterase activity as compared with control, 10 µM and 40 µM lipoic acid-treated cells. 200 µM lipoic acid also caused a significant decrease on PON1 mRNA expression whereas on a significant increase PON3 mRNA expression as compared with control, 10 µM and 40 µM lipoic acid-treated cells. Our study showed that although lipoic acid up-regulates PON3 but down-regulates PON1 mRNA expression, it increases both PON1 and PON3 protein levels and arylesterase activity in HepG2 cells. We can report that lipoic acid may be useful for preventing atherosclerosis at therapeutic doses.

How to cite (APA format):
Ozgun, E, Sayilan Ozgun, G, Tabakcioglu, K, Suer Gokmen, S, Sut, N, Eskiocak, S. (2017). Effect of lipoic acid on paraoxonase-1 and paraoxonase-3 protein levels, mRNA expression and arylesterase activity in liver hepatoma cells. General Physiology and Biophysics, 36(4), 465-470.


 
Evaluation of liposomal carnosine in adjuvant arthritis.
Lukáš Slovák 1), Silvester Poništ, Tatiana Fedorova, Anna Logvinenko, Irina Levacheva, Olga Samsonova, Udo Bakowsky, Ľudmila Pašková, Tomáš Čavojský, Lia Tsiklauri, Katarína Bauerová

1)Institute of Experimental Pharmacology and Toxicology of the Slovak Academy of Sciences, Dúbravská cesta 9, Bratislava, Slovakia. katarina.bauerova@savba.sk.

Liposomal carnosine could overcome the problems associated with direct application of this peptide. Anti-inflammatory and antioxidant effects of liposomal and non-liposomal carnosine in adjuvant arthritis were compared. The experiments were done on healthy animals, untreated arthritic animals, arthritic animals with oral administration of carnosine, and with subcutaneous administration of liposomal carnosine, both administered in the same daily dose of 150 mg/kg b.w. during 28 days. Carnosine reduced hind paw volume on day 28. Both forms markedly decreased interleukin-1β, matrix metalloproteinase-9 and monocyte chemoattractant protein-1 (MCP-1) in plasma on day 14. Only liposomal carnosine reduced significantly MCP-1. Malondialdehyde, 4-hydroxynonenal, resistance to Fe2+-induced oxidation and protein carbonyls were significantly corrected after administration of any form of carnosine. Liposomal carnosine corrected more effectively the oxidative stress in plasma than did carnosine. In brain tissue, our results showed protective ability of both forms of carnosine against oxidation of proteins and lipids. They also corrected the resistance to Fe2+-induced oxidation in arthritic animals. We found that only liposomal carnosine decreased the mRNA expression of inducible nitric oxide synthase in cartilage tissue. It can be concluded that the liposomal drug-delivery system is improving the pharmacological properties of carnosine administered in arthritis.

How to cite (APA format):
Slovák, L, Poništ, S, Fedorova, T, Logvinenko, A, Levacheva, I, Samsonova, O, Bakowsky, U, Pašková, Ľ, Čavojský, T, Tsiklauri, L, Bauerová, K. (2017). Evaluation of liposomal carnosine in adjuvant arthritis. General Physiology and Biophysics, 36(4), 471-479.


 
Effects of natural ligands and synthetic triorganotin compounds of nuclear retinoid X receptors in human MCF-7 breast cancer cell line.
Dana Macejova 1), Lucia Toporova, Július Brtko

1)Laboratory of Molecular Endocrinology, Institute of Experimental Endocrinology, BMC, Slovak Academy of Sciences, Dubravska cesta 9, 845 45 Bratislava, Slovakia. ueenmace@savba.sk.

In the present study, we analyzed in vitro effects of natural and synthetic triorganotin ligands of nuclear retinoid X receptors in human MCF-7 breast cancer cells. Our data has shown that all-trans retinoic acid significantly reduced expression of RXRalpha mRNA, Bcl2 and enhanced expression of BAX proteins. Tributyltin bromide markedly decreased mRNA level of RXRalpha and RXRbeta. Significantly reduced levels of both RXRs proteins were observed after treatment with tributyltin chloride (TBT-Cl) but not after treatment with triphenyltin chloride (TPT-Cl) for RXRbeta protein. Both RXRalpha and RXRbeta protein levels decrease was found also by combination ATRA+TBT-Cl/TPT-Cl.

How to cite (APA format):
Macejova, D, Toporova, L, Brtko, J. (2017). Effects of natural ligands and synthetic triorganotin compounds of nuclear retinoid X receptors in human MCF-7 breast cancer cell line. General Physiology and Biophysics, 36(4), 481-484.