Katalin Sipos | University of Pécs (original) (raw)
Papers by Katalin Sipos
International Journal of Molecular Sciences
Iron is a crucial element in the human body. Endometrial iron metabolism is implicated in endomet... more Iron is a crucial element in the human body. Endometrial iron metabolism is implicated in endometrium receptivity and embryo implantation. Disturbances of the maternal as well as the endometrial iron homeostasis, such as iron deficiency, can contribute to the reduced development of the fetus and could cause an increased risk of adverse pregnancy outcomes. Fractalkine is a unique chemokine that plays a role in the communication between the mother and the fetus. It has been demonstrated that FKN is involved in the development of endometrial receptivity and embryo implantation, and it functions as a regulator of iron metabolism. In the present study, we examined the effect of FKN on the iron metabolism of HEC-1A endometrial cells in a state of iron deficiency mediated by desferrioxamine treatment. Based on the findings, FKN enhances the expression of iron metabolism-related genes in iron deficiency and modifies the iron uptake via transferrin receptor 1 and divalent metal transporter-1...
International Journal of Molecular Sciences
Fractalkine (CX3CL1/FKN) is a unique chemokine belonging to the CX3C chemokine subclass. FKN exis... more Fractalkine (CX3CL1/FKN) is a unique chemokine belonging to the CX3C chemokine subclass. FKN exists in two forms: a membrane-bound form expressed by both endometrium cells and trophoblasts thought to be implicated in maternal–fetal interaction and a soluble form expressed by endometrium cells. Endometrium receptivity is crucial in embryo implantation and a complex process regulated by large numbers of proteins, e.g., cytokines, progesterone receptor (PR), SOX-17, prostaglandin receptors (PTGER2), and tissue inhibitors of metalloproteinases (TIMPs). It has also been reported that iron is important in fertility and affects the iron status of the mother. Therefore, iron availability in the embryo contributes to fertilization and pregnancy. In this study, we focused on the effect of iron deficiency on the secreted cytokines (IL-6, IL-1β, leukocyte inhibitory factor, TGF-β), chemokines (IL-8, FKN), and other regulatory proteins (bone morphogenic protein 2, activin, follistatin, PR, SOX-1...
Orvosi hetilap, Jan 8, 2001
The plasma cell myeloma (multiple myeloma, myelomatosis) is a progressive disease, characterized ... more The plasma cell myeloma (multiple myeloma, myelomatosis) is a progressive disease, characterized by bone marrow plasmacytomas and the presence of monoclonal antibodies (IgG, IgA, IgD, IgE), or free kappa or lambda immunoglobulin side chains. The monoclonal antibodies or Bence-Jones protein may precipitate in the tubuli and impair kidney function. In addition, the plasma protein concentration may increase at the expense of plasma water level causing unrealistically low electrolyte levels. Since the isoelectric points of immunoglobulins are higher than those of most other plasma proteins, the net charge of plasma proteins may change causing new electrolyte balance. In addition, some monoclonal antibodies are more hydrated than others, and their high concentration may cause not only increased plasma viscosity but further electrolyte imbalance. In the present work the relationship between plasma protein and electrolyte levels is studied in samples of 100 multiple myeloma patients.
International Journal of Molecular Sciences
Dietary lutein can be naturally metabolized to 3′-epilutein and 3′-oxolutein in the human body. T... more Dietary lutein can be naturally metabolized to 3′-epilutein and 3′-oxolutein in the human body. The epimerization of lutein can happen in acidic pH, and through cooking, 3′-epilutein can be the product of the direct oxidation of lutein in the retina, which is also present in human serum. The 3′-oxolutein is the main oxidation product of lutein. Thus, the allylic oxidation of dietary lutein can result in the formation of 3′-oxolutein, which may undergo reduction either to revert to dietary lutein or epimerize to form 3′-epilutein. We focused on the effects of 3′-epilutein and 3′-oxolutein itself and on glutamate-induced neurotoxicity on SH-SY5Y human neuroblastoma cells to identify the possible alterations in oxidative stress, inflammation, antioxidant capacity, and iron metabolism that affect neurological function. ROS measurements were performed in the differently treated cells. The inflammatory state of cells was followed by TNFα, IL-6, and IL-8 cytokine ELISA measurements. The an...
Antioxidants
The xanthophyll carotenoid lutein has been widely used as supplementation due to its protective e... more The xanthophyll carotenoid lutein has been widely used as supplementation due to its protective effects in light-induced oxidative stress. Its antioxidant and anti-inflammatory features suggest that it has a neuroprotective role as well. Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS), which plays a key role in regulating brain function. Excess accumulation of intracellular glutamate accelerates an increase in the concentration of reactive oxygen species (ROS) in neurons leading to glutamate neurotoxicity. In this study, we focused on the effects of glutamate on SH-SY5Y neuroblastoma cells to identify the possible alterations in oxidative stress, inflammation, and iron metabolism that affect the neurological function itself and in the presence of antioxidant lutein. First, ROS measurements were performed, and then catalase (CAT) and Superoxide Dismutase (SOD) enzyme activity were determined by enzyme activity assay kits. The ELISA technique was u...
Diabetology & Metabolic Syndrome
Background The hypothalamus of the central nervous system is implicated in the development of dia... more Background The hypothalamus of the central nervous system is implicated in the development of diabetes due to its glucose-sensing function. Dysregulation of the hypothalamic glucose-sensing neurons leads to abnormal glucose metabolism. It has been described that fractalkine (FKN) is involved in the development of hypothalamic inflammation, which may be one of the underlying causes of a diabetic condition. Moreover, iron may play a role in the pathogenesis of diabetes via the regulation of hepcidin, the iron regulatory hormone synthesis. MicroRNAs (miRNAs) are short non-coding molecules working as key regulators of gene expression, usually by inhibiting translation. Hypothalamic miRNAs are supposed to have a role in the control of energy balance by acting as regulators of hypothalamic glucose metabolism via influencing translation. Methods Using a miRNA array, we analysed the expression of diabetes, inflammation, and iron metabolism related miRNAs in the hypothalamus of a streptozoto...
European Journal of Pharmaceutical Sciences
Novel series of cyclic C5-curcuminoids 17a-j and 19-22 were prepared as cytotoxic agents and eval... more Novel series of cyclic C5-curcuminoids 17a-j and 19-22 were prepared as cytotoxic agents and evaluated against human neuroblastoma (SH-SY5Y) or human grade IV astrocytoma (CCF-STTG1) cell lines in low (∼0.1nM - 10nM) concentrations. Among the tested 21 derivatives, 16 displayed potent antiproliferative activity with IC50 values in the low nanomolar to picomolar range (IC50=7.483-0.139 nM). Highly active compounds like N-monocarboxylic derivative 19b with IC50=0.139 nM value against neuroblastoma and N-alkyl substituted 11 with IC50=0.257 nM against astrocytoma proved some degree of selectivity toward non-cancerous astrocytes and kidney cells. This potent anticancer activity did not show a strong correlation with experimental logPTLC values, but the most potent antiproliferative molecules 11-13 and 19-22 are belonging to discrete subgroups of the cyclic C5-curcuminoids. Compounds 12, 17c and 19b were subjected to blood-brain barrier (BBB) penetration studies, too. The BBB was revealed to be permeable for all of them but, as the apparent permeability coefficient (Papp) values mirrored, in different ratios. Lower toxicity of 12, 17c and 19b was observed toward primary rat brain endothelial cells of the BBB model, which means they remained undamaged under 10 µM concentrations. Penetration depends, at least in part, on albumin binding of 12, 17c and 19b and the presence of monocarboxylic acid transporters in the case of 19b. Permeation through the BBB and albumin binding, we described here, is the first example of cyclic C5-curcuminoids as to our knowledge.
Cellular and Molecular Neurobiology, 2018
Cuprizone (CZ) is a widely used copper chelating agent to develop non-autoimmune animal model of ... more Cuprizone (CZ) is a widely used copper chelating agent to develop non-autoimmune animal model of multiple sclerosis, characterized by demyelination of the corpus callosum (CC) and other brain regions. The exact mechanisms of CZ action are still arguable, but it seems that the only affected cells are the mature oligodendrocytes, possibly via metabolic disturbances caused by copper deficiency. During the pathogenesis of multiple sclerosis, high amount of deposited iron can be found throughout the demyelinated areas of the brain in the form of extracellular iron deposits and intracellularly accumulated iron in microglia. In the present study, we used the accepted experimental model of 0.2% CZ-containing diet with standard iron concentration to induce demyelination in the brain of C57BL/6 mice. Our aim was to examine the changes of iron homeostasis in the CC and as a part of the systemic iron regulation, in the liver. Our data showed that CZ treatment changed the iron metabolism of both tissues; however, it had more impact on the liver. Besides the alterations in the expressions of iron storage and import proteins, we detected reduced serum iron concentration and iron stores in the liver, together with elevated hepcidin levels and feasible disturbances in the Fe-S cluster biosynthesis. Our results revealed that the CZ-containing diet influences the systemic iron metabolism in mice, particularly the iron homeostasis of the liver. This inadequate systemic iron regulation may affect the iron homeostasis of the brain, eventually indicating a relationship among CZ treatment, iron metabolism, and neurodegeneration.
The Protein Journal, 2018
Hepcidin, the key hormone of iron homeostasis is responsible for lowering the serum iron level th... more Hepcidin, the key hormone of iron homeostasis is responsible for lowering the serum iron level through its interaction with iron exporter ferroportin. Thus, hepcidin agonists provide a promising opportunity in the treatment of iron disorders caused by lacking or decreased hepcidin expression. We investigated the importance of each of the eight highly conserved cysteines for the biological activity of hepcidin. Eight cysteine mutants were created with site directed mutagenesis. The binding ability of these hepcidin mutants to the hepcidin receptor ferroportin was determined using bacterial two-hybrid system and WRL68 human hepatic cells. The biological activity of hepcidin mutants was determined by western blot analysis of ferroportin internalization and ferroportin ubiquitination. To investigate the effect of mutant hepcidins on the iron metabolism of the WRL68 cells, total intracellular iron content was measured with a colorimetric assay. The stability of M6 hepcidin mutant was determined using ELISA technique. Our data revealed that serine substitution of the sixth cysteine (M6) yielded a biologically active but significantly more stable peptide than the original hormone. This result may provide a promising hepcidin agonist worth testing in animal models.
Is There an Answer? is intended to serve as a forum in which readers to IUBMB Life may pose quest... more Is There an Answer? is intended to serve as a forum in which readers to IUBMB Life may pose questions of the type that intrigue biochemists but for which there may be no obvious answer or one may be available but not widely known or easily accessible. Readers are invited to e-mail f.vella@sasktel.net if they have questions to contribute or
Microbios, 1996
The possibility of coupling along the supply routes of phenylalanine from its uptake by the cell,... more The possibility of coupling along the supply routes of phenylalanine from its uptake by the cell, through the charging of specific tRNAs, has been postulated. The experimental approach to testing this hypothesis has been to study the competition between endogenously synthesized and exogenously supplied amino acids, from which preferences for their incorporation into cellular proteins can be deduced. The results indicate that manipulation of the endogenous phenylalanine pool size, achieved by addition of its immediate precursor, beta-phenylpyruvate, does not cause the predicted changes in the incorporation of exogenous labelled phenylalanine into proteins. The evidence favours exogenous phenylalanine being preferentially delivered to the sites of protein synthesis.
Microbios, 1995
The acid extractable amino acid pool (AEP) demonstrates time and concentration dependent saturati... more The acid extractable amino acid pool (AEP) demonstrates time and concentration dependent saturation kinetics in cold-incubated (0-2 degrees C) Escherichia coli cells. Attention is drawn in particular to the contribution of the AEP to the total non-covalently bound amino acid intracellular levels (total pool) at low exogenous amino acid concentrations. Amino acids compete with one another for associations which internally constitute the AEP. Although physicochemically related amino acids tend to be better competitors than other amino acids, the physicochemical relatedness was by no means the sole, or necessarily the main, factor determining competitiveness. On the return of cells to incubation temperatures allowing protein synthesis to proceed, the contribution of the AEP to protein synthesis was explored.
Journal of Cellular Biochemistry, 1995
The human myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein expressed spec... more The human myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein expressed specifically in cells of the myelomonocytic lineage and regulated by interferon a in a cell-specific fashion. MNDA is also a member of afamily of interferon-regulated genes of unknown function. In an effort to elucidate the function of MNDA, three techniques (affinity purification, coimmunoprecipitation, and protein blot assay) were used to characterize its specific protein binding activities. Microsequence analysis showed that MNDA bound the 100 kDa nucleolin protein. The identification of nucleolin was confirmed by immunoreaction with specific antibodies. MNDA contains motifs which could account for specific binding to nucleolin. Nucleolin binds other macromolecules and exhibits features consistent with roles in signal transduction, production of ribosomes, nuclear matrix structure, and regulation of transcription. The present results indicate that the function of MNDA is most likely related to interactions with other proteins. Through these associations, MNDA could contribute cell/lineageand differentiation-specific limits to the function of ubiquitous proteins such as nucleolin. Further analysis of MNDA protein binding could be critical to elucidating the function of MNDA and could contribute to understanding the function of the products of other members of this interferon-inducible family of genes.
Biochemical and Biophysical Research Communications, 1991
Antioxidants
Thyme (Thymus vulgaris L.) essential oil (TEO) is widely used as an alternative therapy especiall... more Thyme (Thymus vulgaris L.) essential oil (TEO) is widely used as an alternative therapy especially for infections of the upper respiratory tract. TEO possesses antiviral, antibacterial, and antifungal properties. The emerging antibiotic resistance of bacterial strains, including Pseudomonas aeruginosa, has prompted the urge to find alternative treatments. In the present study, we examined the anti-inflammatory and antioxidant effects of thymol, the main compound of TEO, and two TEOs prepared at the beginning and at the end of the flowering period that may make these oils promising candidates as complementary or alternative therapies against P. aeruginosa infections. The activity measurements of the antioxidant enzymes peroxidase (PX), catalase (CAT), and superoxide dismutase (SOD) as well as the determination of total antioxidant capacity of P. aeruginosa-activated THP-1 cells revealed that thymol and both TEOs increased CAT and SOD activity as well as the antioxidant capacity of th...
Experimental Cell Research, 2021
Endometrium receptivity and successful implantation require a complex network of regulatory facto... more Endometrium receptivity and successful implantation require a complex network of regulatory factors whom production is strictly controlled especially at the implantation window. Many regulators like steroid hormones, prostaglandins, cytokines, extracellular matrix proteins and downstream cell signalling pathways are involved in the process of embryo-endometrium interaction. Our work reveals the effect of fractalkine (FKN), a unique chemokine on progesterone receptor, SOX-17 and NRF2 expressions in HEC-1A endometrial cell line. FKN activates fractalkine receptor signalling and the expression of SOX-17 through progesterone receptor in HEC-1A endometrial cells, and as a consequence it increases endometrial receptivity. Fractalkine also activates the NRF2-Keap-1 signal transduction pathway regulating the IL-6 and IL-1β cytokine productions, which increase endometrial receptivity, as well. The NRF2 transcription factor increases the expression of the iron exporter ferroportin in HEC-1A cells activating iron release towards JEG-3 trophoblast cells. The iron measurements show that iron content of endometrial cells decreases while heme concentration increases at FKN treatment. At the same time, the trophoblast cells show increased iron uptake and total iron content. Based on our results it seems that FKN enhances the establishment of endometrial receptivity and meanwhile it regulates the iron homeostasis of endometrium contributing to the iron availability of the trophoblast cells and the embryo.
International Journal of Molecular Sciences, 2022
Fractalkine (CX3CL1) acts as a chemokine as well as a regulator of iron metabolism. Fractalkine b... more Fractalkine (CX3CL1) acts as a chemokine as well as a regulator of iron metabolism. Fractalkine binds CX3CR1, the fractalkine receptor on the surface of monocytes/macrophages regulating different intracellular signalling pathways such as mitogen-activated protein kinase (MAPK), phospholipase C (PLC) and NFκB contributing to the production of pro-inflammatory cytokine synthesis, and the regulation of cell growth, differentiation, proliferation and metabolism. In this study, we focused on the modulatory effects of fractalkine on the immune response and on the iron metabolism of Escherichia coli and Pseudomonas aeruginosa lipopolysaccharides (LPS) and Staphylococcus aureus lipoteichoic acid (LTA) activated THP-1 cells to get a deeper insight into the role of soluble fractalkine in the regulation of the innate immune system. Pro-inflammatory cytokine secretions of the fractalkine-treated, LPS/LTA-treated, and co-treated THP-1 cells were determined using ELISArray and ELISA measurements....
Journal of Forensic and Legal Medicine, 2022
A diagnosis of drowning is not always possible based on the traditional autopsy findings. The mos... more A diagnosis of drowning is not always possible based on the traditional autopsy findings. The most widely used ancillary methods are based on the detection of diatoms and other waterborne organisms in the organs of the systemic circulation by light microscope or polymerase chain reaction (PCR). One of the greatest concerns is sample contamination. Bone marrow is a favourable source because the compact bone protects the sample from water ingress in the case of advanced decay. In our pilot study, we aimed to adopt sternal bone marrow aspiration - which is a widely used technique in haematology - for postmortem sampling. Control experiments of non-drowning victims showed that cleaning the skin over the sternum can prevent external contamination. Sternal aspirate samples were taken from seven suspected drowning victims along with lung, spleen, and femoral bone marrow samples. All specimens were examined for the presence of diatoms by light microscope and Cyanobacteria-specific DNA by PCR. We were able to obtain bone marrow aspirates from all cases without complications. In four of the sternal samples both diatoms and cyanobacterial DNA were detected, while one additional sternum sample was tested positive with PCR, but no diatom shells were detectable. Sternal bone marrow aspiration is simple and quick, which can be performed at the beginning of an autopsy, minimizing the chance of contamination. We have shown that this sampling method can be adopted for postmortem diatom testing. This minimally invasive technique might be used in virtual autopsy (postmortem computed tomography, PMCT) settings without opening body cavities.
International Journal of Molecular Sciences
Iron is a crucial element in the human body. Endometrial iron metabolism is implicated in endomet... more Iron is a crucial element in the human body. Endometrial iron metabolism is implicated in endometrium receptivity and embryo implantation. Disturbances of the maternal as well as the endometrial iron homeostasis, such as iron deficiency, can contribute to the reduced development of the fetus and could cause an increased risk of adverse pregnancy outcomes. Fractalkine is a unique chemokine that plays a role in the communication between the mother and the fetus. It has been demonstrated that FKN is involved in the development of endometrial receptivity and embryo implantation, and it functions as a regulator of iron metabolism. In the present study, we examined the effect of FKN on the iron metabolism of HEC-1A endometrial cells in a state of iron deficiency mediated by desferrioxamine treatment. Based on the findings, FKN enhances the expression of iron metabolism-related genes in iron deficiency and modifies the iron uptake via transferrin receptor 1 and divalent metal transporter-1...
International Journal of Molecular Sciences
Fractalkine (CX3CL1/FKN) is a unique chemokine belonging to the CX3C chemokine subclass. FKN exis... more Fractalkine (CX3CL1/FKN) is a unique chemokine belonging to the CX3C chemokine subclass. FKN exists in two forms: a membrane-bound form expressed by both endometrium cells and trophoblasts thought to be implicated in maternal–fetal interaction and a soluble form expressed by endometrium cells. Endometrium receptivity is crucial in embryo implantation and a complex process regulated by large numbers of proteins, e.g., cytokines, progesterone receptor (PR), SOX-17, prostaglandin receptors (PTGER2), and tissue inhibitors of metalloproteinases (TIMPs). It has also been reported that iron is important in fertility and affects the iron status of the mother. Therefore, iron availability in the embryo contributes to fertilization and pregnancy. In this study, we focused on the effect of iron deficiency on the secreted cytokines (IL-6, IL-1β, leukocyte inhibitory factor, TGF-β), chemokines (IL-8, FKN), and other regulatory proteins (bone morphogenic protein 2, activin, follistatin, PR, SOX-1...
Orvosi hetilap, Jan 8, 2001
The plasma cell myeloma (multiple myeloma, myelomatosis) is a progressive disease, characterized ... more The plasma cell myeloma (multiple myeloma, myelomatosis) is a progressive disease, characterized by bone marrow plasmacytomas and the presence of monoclonal antibodies (IgG, IgA, IgD, IgE), or free kappa or lambda immunoglobulin side chains. The monoclonal antibodies or Bence-Jones protein may precipitate in the tubuli and impair kidney function. In addition, the plasma protein concentration may increase at the expense of plasma water level causing unrealistically low electrolyte levels. Since the isoelectric points of immunoglobulins are higher than those of most other plasma proteins, the net charge of plasma proteins may change causing new electrolyte balance. In addition, some monoclonal antibodies are more hydrated than others, and their high concentration may cause not only increased plasma viscosity but further electrolyte imbalance. In the present work the relationship between plasma protein and electrolyte levels is studied in samples of 100 multiple myeloma patients.
International Journal of Molecular Sciences
Dietary lutein can be naturally metabolized to 3′-epilutein and 3′-oxolutein in the human body. T... more Dietary lutein can be naturally metabolized to 3′-epilutein and 3′-oxolutein in the human body. The epimerization of lutein can happen in acidic pH, and through cooking, 3′-epilutein can be the product of the direct oxidation of lutein in the retina, which is also present in human serum. The 3′-oxolutein is the main oxidation product of lutein. Thus, the allylic oxidation of dietary lutein can result in the formation of 3′-oxolutein, which may undergo reduction either to revert to dietary lutein or epimerize to form 3′-epilutein. We focused on the effects of 3′-epilutein and 3′-oxolutein itself and on glutamate-induced neurotoxicity on SH-SY5Y human neuroblastoma cells to identify the possible alterations in oxidative stress, inflammation, antioxidant capacity, and iron metabolism that affect neurological function. ROS measurements were performed in the differently treated cells. The inflammatory state of cells was followed by TNFα, IL-6, and IL-8 cytokine ELISA measurements. The an...
Antioxidants
The xanthophyll carotenoid lutein has been widely used as supplementation due to its protective e... more The xanthophyll carotenoid lutein has been widely used as supplementation due to its protective effects in light-induced oxidative stress. Its antioxidant and anti-inflammatory features suggest that it has a neuroprotective role as well. Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS), which plays a key role in regulating brain function. Excess accumulation of intracellular glutamate accelerates an increase in the concentration of reactive oxygen species (ROS) in neurons leading to glutamate neurotoxicity. In this study, we focused on the effects of glutamate on SH-SY5Y neuroblastoma cells to identify the possible alterations in oxidative stress, inflammation, and iron metabolism that affect the neurological function itself and in the presence of antioxidant lutein. First, ROS measurements were performed, and then catalase (CAT) and Superoxide Dismutase (SOD) enzyme activity were determined by enzyme activity assay kits. The ELISA technique was u...
Diabetology & Metabolic Syndrome
Background The hypothalamus of the central nervous system is implicated in the development of dia... more Background The hypothalamus of the central nervous system is implicated in the development of diabetes due to its glucose-sensing function. Dysregulation of the hypothalamic glucose-sensing neurons leads to abnormal glucose metabolism. It has been described that fractalkine (FKN) is involved in the development of hypothalamic inflammation, which may be one of the underlying causes of a diabetic condition. Moreover, iron may play a role in the pathogenesis of diabetes via the regulation of hepcidin, the iron regulatory hormone synthesis. MicroRNAs (miRNAs) are short non-coding molecules working as key regulators of gene expression, usually by inhibiting translation. Hypothalamic miRNAs are supposed to have a role in the control of energy balance by acting as regulators of hypothalamic glucose metabolism via influencing translation. Methods Using a miRNA array, we analysed the expression of diabetes, inflammation, and iron metabolism related miRNAs in the hypothalamus of a streptozoto...
European Journal of Pharmaceutical Sciences
Novel series of cyclic C5-curcuminoids 17a-j and 19-22 were prepared as cytotoxic agents and eval... more Novel series of cyclic C5-curcuminoids 17a-j and 19-22 were prepared as cytotoxic agents and evaluated against human neuroblastoma (SH-SY5Y) or human grade IV astrocytoma (CCF-STTG1) cell lines in low (∼0.1nM - 10nM) concentrations. Among the tested 21 derivatives, 16 displayed potent antiproliferative activity with IC50 values in the low nanomolar to picomolar range (IC50=7.483-0.139 nM). Highly active compounds like N-monocarboxylic derivative 19b with IC50=0.139 nM value against neuroblastoma and N-alkyl substituted 11 with IC50=0.257 nM against astrocytoma proved some degree of selectivity toward non-cancerous astrocytes and kidney cells. This potent anticancer activity did not show a strong correlation with experimental logPTLC values, but the most potent antiproliferative molecules 11-13 and 19-22 are belonging to discrete subgroups of the cyclic C5-curcuminoids. Compounds 12, 17c and 19b were subjected to blood-brain barrier (BBB) penetration studies, too. The BBB was revealed to be permeable for all of them but, as the apparent permeability coefficient (Papp) values mirrored, in different ratios. Lower toxicity of 12, 17c and 19b was observed toward primary rat brain endothelial cells of the BBB model, which means they remained undamaged under 10 µM concentrations. Penetration depends, at least in part, on albumin binding of 12, 17c and 19b and the presence of monocarboxylic acid transporters in the case of 19b. Permeation through the BBB and albumin binding, we described here, is the first example of cyclic C5-curcuminoids as to our knowledge.
Cellular and Molecular Neurobiology, 2018
Cuprizone (CZ) is a widely used copper chelating agent to develop non-autoimmune animal model of ... more Cuprizone (CZ) is a widely used copper chelating agent to develop non-autoimmune animal model of multiple sclerosis, characterized by demyelination of the corpus callosum (CC) and other brain regions. The exact mechanisms of CZ action are still arguable, but it seems that the only affected cells are the mature oligodendrocytes, possibly via metabolic disturbances caused by copper deficiency. During the pathogenesis of multiple sclerosis, high amount of deposited iron can be found throughout the demyelinated areas of the brain in the form of extracellular iron deposits and intracellularly accumulated iron in microglia. In the present study, we used the accepted experimental model of 0.2% CZ-containing diet with standard iron concentration to induce demyelination in the brain of C57BL/6 mice. Our aim was to examine the changes of iron homeostasis in the CC and as a part of the systemic iron regulation, in the liver. Our data showed that CZ treatment changed the iron metabolism of both tissues; however, it had more impact on the liver. Besides the alterations in the expressions of iron storage and import proteins, we detected reduced serum iron concentration and iron stores in the liver, together with elevated hepcidin levels and feasible disturbances in the Fe-S cluster biosynthesis. Our results revealed that the CZ-containing diet influences the systemic iron metabolism in mice, particularly the iron homeostasis of the liver. This inadequate systemic iron regulation may affect the iron homeostasis of the brain, eventually indicating a relationship among CZ treatment, iron metabolism, and neurodegeneration.
The Protein Journal, 2018
Hepcidin, the key hormone of iron homeostasis is responsible for lowering the serum iron level th... more Hepcidin, the key hormone of iron homeostasis is responsible for lowering the serum iron level through its interaction with iron exporter ferroportin. Thus, hepcidin agonists provide a promising opportunity in the treatment of iron disorders caused by lacking or decreased hepcidin expression. We investigated the importance of each of the eight highly conserved cysteines for the biological activity of hepcidin. Eight cysteine mutants were created with site directed mutagenesis. The binding ability of these hepcidin mutants to the hepcidin receptor ferroportin was determined using bacterial two-hybrid system and WRL68 human hepatic cells. The biological activity of hepcidin mutants was determined by western blot analysis of ferroportin internalization and ferroportin ubiquitination. To investigate the effect of mutant hepcidins on the iron metabolism of the WRL68 cells, total intracellular iron content was measured with a colorimetric assay. The stability of M6 hepcidin mutant was determined using ELISA technique. Our data revealed that serine substitution of the sixth cysteine (M6) yielded a biologically active but significantly more stable peptide than the original hormone. This result may provide a promising hepcidin agonist worth testing in animal models.
Is There an Answer? is intended to serve as a forum in which readers to IUBMB Life may pose quest... more Is There an Answer? is intended to serve as a forum in which readers to IUBMB Life may pose questions of the type that intrigue biochemists but for which there may be no obvious answer or one may be available but not widely known or easily accessible. Readers are invited to e-mail f.vella@sasktel.net if they have questions to contribute or
Microbios, 1996
The possibility of coupling along the supply routes of phenylalanine from its uptake by the cell,... more The possibility of coupling along the supply routes of phenylalanine from its uptake by the cell, through the charging of specific tRNAs, has been postulated. The experimental approach to testing this hypothesis has been to study the competition between endogenously synthesized and exogenously supplied amino acids, from which preferences for their incorporation into cellular proteins can be deduced. The results indicate that manipulation of the endogenous phenylalanine pool size, achieved by addition of its immediate precursor, beta-phenylpyruvate, does not cause the predicted changes in the incorporation of exogenous labelled phenylalanine into proteins. The evidence favours exogenous phenylalanine being preferentially delivered to the sites of protein synthesis.
Microbios, 1995
The acid extractable amino acid pool (AEP) demonstrates time and concentration dependent saturati... more The acid extractable amino acid pool (AEP) demonstrates time and concentration dependent saturation kinetics in cold-incubated (0-2 degrees C) Escherichia coli cells. Attention is drawn in particular to the contribution of the AEP to the total non-covalently bound amino acid intracellular levels (total pool) at low exogenous amino acid concentrations. Amino acids compete with one another for associations which internally constitute the AEP. Although physicochemically related amino acids tend to be better competitors than other amino acids, the physicochemical relatedness was by no means the sole, or necessarily the main, factor determining competitiveness. On the return of cells to incubation temperatures allowing protein synthesis to proceed, the contribution of the AEP to protein synthesis was explored.
Journal of Cellular Biochemistry, 1995
The human myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein expressed spec... more The human myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein expressed specifically in cells of the myelomonocytic lineage and regulated by interferon a in a cell-specific fashion. MNDA is also a member of afamily of interferon-regulated genes of unknown function. In an effort to elucidate the function of MNDA, three techniques (affinity purification, coimmunoprecipitation, and protein blot assay) were used to characterize its specific protein binding activities. Microsequence analysis showed that MNDA bound the 100 kDa nucleolin protein. The identification of nucleolin was confirmed by immunoreaction with specific antibodies. MNDA contains motifs which could account for specific binding to nucleolin. Nucleolin binds other macromolecules and exhibits features consistent with roles in signal transduction, production of ribosomes, nuclear matrix structure, and regulation of transcription. The present results indicate that the function of MNDA is most likely related to interactions with other proteins. Through these associations, MNDA could contribute cell/lineageand differentiation-specific limits to the function of ubiquitous proteins such as nucleolin. Further analysis of MNDA protein binding could be critical to elucidating the function of MNDA and could contribute to understanding the function of the products of other members of this interferon-inducible family of genes.
Biochemical and Biophysical Research Communications, 1991
Antioxidants
Thyme (Thymus vulgaris L.) essential oil (TEO) is widely used as an alternative therapy especiall... more Thyme (Thymus vulgaris L.) essential oil (TEO) is widely used as an alternative therapy especially for infections of the upper respiratory tract. TEO possesses antiviral, antibacterial, and antifungal properties. The emerging antibiotic resistance of bacterial strains, including Pseudomonas aeruginosa, has prompted the urge to find alternative treatments. In the present study, we examined the anti-inflammatory and antioxidant effects of thymol, the main compound of TEO, and two TEOs prepared at the beginning and at the end of the flowering period that may make these oils promising candidates as complementary or alternative therapies against P. aeruginosa infections. The activity measurements of the antioxidant enzymes peroxidase (PX), catalase (CAT), and superoxide dismutase (SOD) as well as the determination of total antioxidant capacity of P. aeruginosa-activated THP-1 cells revealed that thymol and both TEOs increased CAT and SOD activity as well as the antioxidant capacity of th...
Experimental Cell Research, 2021
Endometrium receptivity and successful implantation require a complex network of regulatory facto... more Endometrium receptivity and successful implantation require a complex network of regulatory factors whom production is strictly controlled especially at the implantation window. Many regulators like steroid hormones, prostaglandins, cytokines, extracellular matrix proteins and downstream cell signalling pathways are involved in the process of embryo-endometrium interaction. Our work reveals the effect of fractalkine (FKN), a unique chemokine on progesterone receptor, SOX-17 and NRF2 expressions in HEC-1A endometrial cell line. FKN activates fractalkine receptor signalling and the expression of SOX-17 through progesterone receptor in HEC-1A endometrial cells, and as a consequence it increases endometrial receptivity. Fractalkine also activates the NRF2-Keap-1 signal transduction pathway regulating the IL-6 and IL-1β cytokine productions, which increase endometrial receptivity, as well. The NRF2 transcription factor increases the expression of the iron exporter ferroportin in HEC-1A cells activating iron release towards JEG-3 trophoblast cells. The iron measurements show that iron content of endometrial cells decreases while heme concentration increases at FKN treatment. At the same time, the trophoblast cells show increased iron uptake and total iron content. Based on our results it seems that FKN enhances the establishment of endometrial receptivity and meanwhile it regulates the iron homeostasis of endometrium contributing to the iron availability of the trophoblast cells and the embryo.
International Journal of Molecular Sciences, 2022
Fractalkine (CX3CL1) acts as a chemokine as well as a regulator of iron metabolism. Fractalkine b... more Fractalkine (CX3CL1) acts as a chemokine as well as a regulator of iron metabolism. Fractalkine binds CX3CR1, the fractalkine receptor on the surface of monocytes/macrophages regulating different intracellular signalling pathways such as mitogen-activated protein kinase (MAPK), phospholipase C (PLC) and NFκB contributing to the production of pro-inflammatory cytokine synthesis, and the regulation of cell growth, differentiation, proliferation and metabolism. In this study, we focused on the modulatory effects of fractalkine on the immune response and on the iron metabolism of Escherichia coli and Pseudomonas aeruginosa lipopolysaccharides (LPS) and Staphylococcus aureus lipoteichoic acid (LTA) activated THP-1 cells to get a deeper insight into the role of soluble fractalkine in the regulation of the innate immune system. Pro-inflammatory cytokine secretions of the fractalkine-treated, LPS/LTA-treated, and co-treated THP-1 cells were determined using ELISArray and ELISA measurements....
Journal of Forensic and Legal Medicine, 2022
A diagnosis of drowning is not always possible based on the traditional autopsy findings. The mos... more A diagnosis of drowning is not always possible based on the traditional autopsy findings. The most widely used ancillary methods are based on the detection of diatoms and other waterborne organisms in the organs of the systemic circulation by light microscope or polymerase chain reaction (PCR). One of the greatest concerns is sample contamination. Bone marrow is a favourable source because the compact bone protects the sample from water ingress in the case of advanced decay. In our pilot study, we aimed to adopt sternal bone marrow aspiration - which is a widely used technique in haematology - for postmortem sampling. Control experiments of non-drowning victims showed that cleaning the skin over the sternum can prevent external contamination. Sternal aspirate samples were taken from seven suspected drowning victims along with lung, spleen, and femoral bone marrow samples. All specimens were examined for the presence of diatoms by light microscope and Cyanobacteria-specific DNA by PCR. We were able to obtain bone marrow aspirates from all cases without complications. In four of the sternal samples both diatoms and cyanobacterial DNA were detected, while one additional sternum sample was tested positive with PCR, but no diatom shells were detectable. Sternal bone marrow aspiration is simple and quick, which can be performed at the beginning of an autopsy, minimizing the chance of contamination. We have shown that this sampling method can be adopted for postmortem diatom testing. This minimally invasive technique might be used in virtual autopsy (postmortem computed tomography, PMCT) settings without opening body cavities.