18 results on '"Zagajewski J"'
Search Results
2. PROPERTY OF A NEW PRUSSIAN BLUE-BOUNDED IRON COMPLEX ABLE TO PEROXIDATE NON-SATURATED FATTY ACIDS WITH A TENDENCY TO CREATE CONDITIONS THAT MAY ENCOURAGE FERROPTOSIS.
- Author
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LASOTA, M., RYBARSKA, J., KONIECZNY, L., ZEMANEK, G., ZAGAJEWSKI, J., CHLOPAS, K., JANKOWSKI, D., KOSCIK, I., SKULSKA-BIRGIEL, A., WISNIEWSKA, A., ICIEK, M., JASEK-GAJDA, E., JASINSKA, M., and JAGUSIAK, A.
- Subjects
FATTY acids ,UNSATURATED fatty acids ,CELL death ,REACTIVE oxygen species ,IRON - Abstract
Ferroptosis is a cell death process caused by redox imbalance in the cell environment. However, the cell death pathway proves beneficial in anticancer therapy, so compounds inducing ferroptosis are sought. The paper presents a newly synthesized iron complex named FeT, composed of ferricyanide and tartrate, which seems to meet these expectations. It is relatively stable, easily soluble in water and capable of peroxidating unsaturated fatty acids. T24 bladder cells were used as model cells. Preliminary studies demonstrated a strong inhibitory effect of this compound on cell proliferation. The cytotoxicity of FeT was assessed. Independently, it initiates caspase activity, indicating the complex cellular impact of this compound. This effect is compellingly the result of FeT penetration into the cell's interior with possible direct damage to mitochondria, thus explaining the involvement of apoptosis in cell death. At the same time, after penetrating into the cell, it causes an increase in reactive oxygen species (ROS), lipid peroxidation and a decrease in reduced glutathione, which is interpreted as to cause ferroptosis. In turn, reducing mitochondrial potential may indicate both ferroptosis and an internal pathway to apoptosis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
3. Proangiogenic activity of beta-carotene is coupled with the activation of endothelial cell chemotaxis
- Author
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Dembinska-Kiec, A., Polus, A., Kiec-Wilk, B., Grzybowska, J., Mikolajczyk, M., Hartwich, J., Razny, U., Szumilas, K., Banas, A., Bodzioch, M., Stachura, J., Dyduch, G., Laidler, P., Zagajewski, J., Langman, T., and Schmitz, G.
- Published
- 2005
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4. SIMULTANEOUS DETECTION OF MELATONIN AND SIX METABOLITES OF L-TRYPTOPHAN PATHWAY IN RAT GASTRIC MUCOSA.
- Author
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ZAGAJEWSKI, J., WOJCIK-GRZYBEK, D., BRZOZOWSKI, B., MAJKA, J., MAGIEROWSKI, M., PLACHA, W., LASOTA, M., LAIDLER, P. M., and BRZOZOWSKI, T.
- Abstract
Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine synthesized in vertebrates mainly in the pineal gland, and is known to be involved mainly in thermoregulation and control of the circadian rhythm. That indoleamine can affect the auto-, para- and endocrine pathways, regulating body functions and affecting the metabolism of animals and humans. In addition to the pineal gland, melatonin can be synthesized in many extra-pineal tissues, mainly in the gastrointestinal tract. Previous studies have shown that melatonin plays an important role in the defense system of the gastrointestinal mucosa, demonstrating a protective effect on the gastrointestinal tract and the acceleration of healing of chronic ulcers through the scavenging of reactive oxygen metabolites (ROS) and the activation of protective nitric oxide (NO) and vasodilator neuropeptides released from the sensory afferent neurons. The process of converting the melatonin precursor L-tryptophan into melatonin is already known, but not all aspects of this process for the synthesis of other metabolites of this pathway have been fully elucidated and this issue remains poorly understood. In this study, the conversion of L-tryptophan to melatonin and other metabolites was determined in gastric mucosa collected from rats with or without intragastric (i.g.) melatonin or L-tryptophan administration, both administered at a single dose of 50 mg/kg. For the determination of five metabolites of L-tryptophan: kynurenine, 5-hydroxytryptamine, 5-hydroxytryptophan, anthranilic acid, indole-3-acetic acid together with melatonin, we have modified the previously developed high-performance liquid chromatography (HPLC) method using a native fluorescence detection system and UV-VIS. The obtained results show that: 1) L-tryptophan is converted into melatonin in the gastric mucosa during the day, e.g. after eating a meal containing L-tryptophan, as it was imitated and confirmed by our study, in which this amino acid was administered directly to the stomach, 2) the gastric mucosa is capable of producing melatonin in much greater amounts than those recorded in the blood serum of rats given a single dose of L-tryptophan, and 3) apart from melatonin, the only serum levels of these five metabolites of the L-tryptophan metabolic pathway are detectable, while their level in the gastric mucosa is low and barely detectable under physiological conditions. Our present observations support the notion that the gastric mucosa is one of the main sources of melatonin production from L-tryptophan outside the pineal gland. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
5. SMALL-MOLECULE INHIBITOR - TYRPHOSTIN AG1296 REGULATES PROLIFERATION, SURVIVAL AND MIGRATION OF RHABDOMYOSARCOMA CELLS.
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LASOTA, M., BENTKE-IMIOLEK, A., SKRZYPEK, K., BOBROWSKA, J., JAGUSIAK, A., BRYNIARSKA-KUBIAK, N., ZAGAJEWSKI, J., KOT, M., SZYDLAK, R., LEKKA, M., LAIDLER, P., and MAJKA, M.
- Subjects
CELL migration ,PLATELET-derived growth factor receptors ,PLATELET-derived growth factor ,SOFT tissue tumors ,PROTEIN-tyrosine kinase inhibitors ,KINASES - Abstract
Rhabdomyosarcoma (RMS) is the most commonly occurring malignant soft tissue tumor in children. Despite improving its treatment methods, the current outcome in the advanced stages of this tumor is not satisfactory. RMS cells are characterized by abnormal cellular signaling due to the changes in the activity of the tyrosine kinases. Thus, substances blocking the mitogenic signal transmitted by receptors with tyrosine kinase activity raise hopes for inhibition of the uncontrolled cell growth. In this study, we examined the anticancer activity of tyrphostin AG1296, a tyrosine kinase inhibitor that binds to the intracellular domain of the PDGF (platelet-derived growth factor) receptor in human RMS alveolar and embryonal cell lines. We have discovered that tyrphostin AG1296 completely inhibited cell proliferation and effectively inhibited cell viability. Tyrphostin AG1296 induced apoptosis of the RMS cells and significantly inhibited their migration. Additionally, investigated inhibitor slightly inhibited expression of AKT and phosphorylation of ERK in alveolar RMS cells. Importantly, the inhibitor exerted also potent effects on the nanomechanical properties and cytoskeleton organization of RMS cells. To conclude, tyrphostin AG1296 is a promising compound in the treatment of alveolar RMS. Undoubtedly, a better knowledge of receptor pathomechanism of tyrosine kinases may contribute to developing new, more effective ways of RMS treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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6. Association of insulin resistance with carotid intima-media thickness and brachial flow-mediated dilation in the subjects with metabolic syndrome
- Author
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Domagala, T., primary, Janczura, M., additional, Kotula-Horowitz, K., additional, Dropinski, J., additional, Iwaniec, T., additional, Zagajewski, J., additional, and Stanisz, A., additional
- Published
- 2016
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7. The chemotactic activity of beta-carotene in endothelial cell progenitors and human umbilical vein endothelial cells: A microarray analysis
- Author
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Polus, A., Kiec-Wilk, B., Hartwich, J., Balwierz, A., Stachura, J., Dyduch, G., Laidler, P., Zagajewski, J., Langman, T., Schmitz, G., Goralczyk, R., Wertz, K., Riss, G., Jaap Keijer, and Dembinska-Kiec, A.
- Subjects
Beta-carotene ,Human and Animal Physiology ,Chemotaxis ,RIKILT - Business Unit Veiligheid & Gezondheid ,Belgrade Satellite Symposium ,RIKILT - Business Unit Safety & Health ,Fysiologie van Mens en Dier ,Angiogenesis ,Endothelium ,Microarray - Abstract
Objectives: Endothelial cells and their progenitors play an important role in angiogenesis that is essential for organogenesis and tissue remodelling, as well as for inflammatory responses and carcinogenesis in all periods of life. In the present study, the authors concentrated on the direct effect of beta-carotene (BC) on human umbilical cord-originated endothelial progenitor cells and human umbilical vein endothelial cells. Methods: BC uptake was measured using high-performance liquid chromatography. The effect on cell proliferation was measured based on bromodeoxyuridine incorporation. Chemotaxis was performed in a Boyden chamber. The influence on tubular-like structure formation was investigated using a three-dimensional assay in Matriget (Becton Dickinson, USA) both in an in vitro and in vivo model. Changes in gene expression were analyzed using the microarray hybridization method. Quantitative gene expression was estimated using the real-time polymerase chain reaction method. Results: It was shown that BC, in the physiological range of concentrations found in human blood, is a potent activator of chemotaxis of endothelial cells. Microarray data analysis revealed that the genes involved in cell-cell and cell-matrix adhesion, matrix reorganization and activation of chemotaxis were the most affected by BC genes in human umbilical vein endothelial cells and endothelial progenitor cells. These results were also confirmed in an in vivo angiogenesis model. Conclusion: BC, in the range of physiological concentrations, stimulates early steps of angiogenic activity of endothelial cells by activation of cellular migration, as well as by matrix reorganization and a decrease in cellular adhesion
- Published
- 2006
8. The impact of cigarette smoking on the pleiotropic effects of simvastatin in the coronary heart disease patients
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Domagala, T.B., primary, Kotula-Horowitz, K., additional, Janczura, M., additional, Januszek, R., additional, Zagajewski, J., additional, and Musial, J., additional
- Published
- 2014
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9. Impact of Q192R of PON1 polymorphism on the endothelial function and oxidative stress markers in the simvastatin-treated CHD patients
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Domagala, T.B., primary, Januszek, R., additional, Kotula-Horowitz, K., additional, Zagajewski, J., additional, Janczura, M., additional, and Musial, J., additional
- Published
- 2014
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10. The Influence of β-Carotene and Its Liposomal Form on the Expression of EMT Markers and Androgen-Dependent Pathways in Different Prostate Cell Lines.
- Author
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Dulińska-Litewka J, Dykas K, Boznański S, Hałubiec P, Kaczor-Kamińska M, Zagajewski J, Bohn T, and Wątor G
- Abstract
Prostate cancer (PCa) is the most common malignancy in men. Although the prognosis in the early stages is good, the treatment of advanced PCa remains a formidable challenge. Even after an initial response to hormone therapy or chemotherapy, recurrences are frequent and resistance to any systemic treatment is common. β-Carotene (BC), a plant-derived tetraterpene, is known for its antioxidant capacity and can modulate multiple cellular signaling pathways, potentially affecting androgen synthesis. We investigated the influence of BC (dissolved in EtOH/THF with a cell culture medium or encapsulated in liposomes (LP-BCs)) on the viability, migration potential, and connective tissue cleavage capabilities of several PCa cell lines (Du145, LNCaP, PC-3, and 22Rv1) and a healthy prostate model (RWPE cells). BC significantly reduced the proliferative capacity of all investigated cell lines at various concentrations (1.5-30 µM) and decreased cell migration. However, it significantly increased the expression of epidermal-mesenchymal transition (EMT) master proteins in all cancer cell lines and RWPE ( p < 0.05) These effects were not observed with LP-BCs. This study suggests that LP-BCs, with their higher antiproliferative capabilities and pronounced inhibition of the EMT, may be a more effective form of possible PCa prevention or treatment than the free form. LPs may also modulate lipid metabolism in PCa cells.
- Published
- 2024
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11. The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma.
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Placha W, Suder P, Panek A, Bronowicka-Adamska P, Zarzycka M, Szczygieł M, Zagajewski J, and Piwowar MW
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- Animals, Mice, Humans, Docetaxel pharmacology, Drug Resistance, Neoplasm, Paclitaxel pharmacology, Cell Line, Tumor, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Melanoma drug therapy
- Abstract
Despite the development of modern drugs, drug resistance in oncology remains the main factor limiting the curability of patients. This paper shows the use of a group of hydrophobic statins to inhibit drug resistance (Pgp protein). In a chemoresistance melanoma cell model, viability, necroptosis with DNA damage, the absorption of the applied pharmaceuticals, and the functional activity of the ABCB1 drug transporter after administration of docetaxel or docetaxel with a selected hydrophobic statin were studied. Taxol-resistant human melanoma cells from three stages of development were used as a model: both A375P and WM239A metastatic lines and radial growth phase WM35 cells. An animal model ( Mus musculus SCID) was developed for the A375P cell line. The results show that hydrophobic statins administered with docetaxel increase the accumulation of the drug in the tumor cell a.o. by blocking the ABCB1 channel. They reduce taxol-induced drug resistance. The tumor size reduction was observed after the drug combination was administrated. It was shown that the structural similarity of statins is of secondary importance, e.g., pravastatin and simvastatin. Using cytostatics in the presence of hydrophobic statins increases their effectiveness while reducing their overall toxicity.
- Published
- 2023
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12. Yohimbine Alleviates Oxidative Stress and Suppresses Aerobic Cysteine Metabolism Elevated in the Rat Liver of High-Fat Diet-Fed Rats.
- Author
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Iciek M, Górny M, Kotańska M, Bilska-Wilkosz A, Kaczor-Kamińska M, and Zagajewski J
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- Male, Rats, Animals, Yohimbine, Diet, High-Fat, Oxidative Stress, Sulfur metabolism, Liver, Sulfur Compounds pharmacology, Obesity metabolism, Cysteine metabolism, Thiosulfate Sulfurtransferase metabolism, Thiosulfate Sulfurtransferase pharmacology
- Abstract
Yohimbine is a small indole alkaloid derived from the bark of the yohimbe tree with documented biological activity, including anti-inflammatory, erectile dysfunction relieving, and fat-burning properties. Hydrogen sulfide (H
2 S) and sulfane sulfur-containing compounds are regarded as important molecules in redox regulation and are involved in many physiological processes. Recently, their role in the pathophysiology of obesity and obesity-induced liver injury was also reported. The aim of the present study was to verify whether the mechanism of biological activity of yohimbine is related to reactive sulfur species formed during cysteine catabolism. We tested the effect of yohimbine at doses of 2 and 5 mg/kg/day administered for 30 days on aerobic and anaerobic catabolism of cysteine and oxidative processes in the liver of high-fat diet (HFD)-induced obese rats. Our study revealed that HFD resulted in a decrease in cysteine and sulfane sulfur levels in the liver, while sulfates were elevated. In the liver of obese rats, rhodanese expression was diminished while lipid peroxidation increased. Yohimbine did not influence sulfane sulfur and thiol levels in the liver of obese rats, however, this alkaloid at a dose of 5 mg decreased sulfates to the control level and induced expression of rhodanese. Moreover, it diminished hepatic lipid peroxidation. It can be concluded that HFD attenuates anaerobic and enhances aerobic cysteine catabolism and induces lipid peroxidation in the rat liver. Yohimbine at a dose of 5 mg/kg can alleviate oxidative stress and reduce elevated concentrations of sulfate probably by the induction of TST expression.- Published
- 2023
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13. Melatonin in Prevention of the Sequence from Reflux Esophagitis to Barrett's Esophagus and Esophageal Adenocarcinoma: Experimental and Clinical Perspectives.
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Majka J, Wierdak M, Brzozowska I, Magierowski M, Szlachcic A, Wojcik D, Kwiecien S, Magierowska K, Zagajewski J, and Brzozowski T
- Subjects
- Animals, Esophagus drug effects, Esophagus metabolism, Esophagus pathology, Humans, Melatonin metabolism, Melatonin pharmacology, Models, Biological, Protective Agents pharmacology, Protective Agents therapeutic use, Adenocarcinoma prevention & control, Barrett Esophagus prevention & control, Esophageal Neoplasms prevention & control, Esophagitis, Peptic prevention & control, Melatonin therapeutic use
- Abstract
Melatonin is a tryptophan-derived molecule with pleiotropic activities which is produced in all living organisms. This "sleep" hormone is a free radical scavenger, which activates several anti-oxidative enzymes and mechanisms. Melatonin, a highly lipophilic hormone, can reach body target cells rapidly, acting as the circadian signal to alter numerous physiological functions in the body. This indoleamine can protect the organs against a variety of damaging agents via multiple signaling. This review focused on the role played by melatonin in the mechanism of esophagoprotection, starting with its short-term protection against acute reflux esophagitis and then investigating the long-term prevention of chronic inflammation that leads to gastroesophageal reflux disease (GERD) and Barrett's esophagus. Since both of these condition are also identified as major risk factors for esophageal carcinoma, we provide some experimental and clinical evidence that supplementation therapy with melatonin could be useful in esophageal injury by protecting various animal models and patients with GERD from erosions, Barrett's esophagus and neoplasia. The physiological aspects of the synthesis and release of this indoleamine in the gut, including its release into portal circulation and liver uptake is examined. The beneficial influence of melatonin in preventing esophageal injury from acid-pepsin and acid-pepsin-bile exposure in animals as well as the usefulness of melatonin and its precursor, L-tryptophan in prophylactic and supplementary therapy against esophageal disorders in humans, are also discussed.
- Published
- 2018
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14. An application of RP-HPLC for determination of the activity of cystathionine β-synthase and γ-cystathionase in tissue homogenates.
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Bronowicka-Adamska P, Zagajewski J, and Wróbel M
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- Alkynes analysis, Alkynes metabolism, Animals, Chromatography, Reverse-Phase, Cystathionine beta-Synthase metabolism, Cystathionine gamma-Lyase metabolism, Cysteine analysis, Cysteine metabolism, Glutathione Disulfide analysis, Glutathione Disulfide metabolism, Glycine analogs & derivatives, Glycine analysis, Glycine metabolism, Homoserine, Mice, Organ Specificity, Chromatography, High Pressure Liquid methods, Cystathionine beta-Synthase analysis, Cystathionine gamma-Lyase analysis
- Abstract
The RP-HPLC-based method of determination of the activity of cystathionine β-synthase and γ-cystathionase was undertaken in mouse liver, kidney and brain. Products of the reactions, such as cystathionine, α-ketobutyrate, cysteine and glutathione, were measured using the RP-HPLC method. A difference in the cystathionine level between homogenates with totally CTH-inhibiting concentrations of DL-propargylglycine and without the inhibitor was employed to evaluate the activity of cystathionine β-synthase. Gamma-cystathionase activity was measured using DL-homoserine as a substrate and a sensitive HPLC-based assay to measure α-ketobutyrate. The results confirmed high cystathionine β-synthase activity and no γ-cystathionase activity in brain, and high γ-cystathionase activity in mouse liver. The method presented here allows for evaluating the relative contribution of CBS and CTH to generation of H2S in tissues. Additionally, it provides results, which reflect the redox status (GSH/GSSG) of a tissue., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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15. Conversion L-tryptophan to melatonin in the gastrointestinal tract: the new high performance liquid chromatography method enabling simultaneous determination of six metabolites of L-tryptophan by native fluorescence and UV-VIS detection.
- Author
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Zagajewski J, Drozdowicz D, Brzozowska I, Hubalewska-Mazgaj M, Stelmaszynska T, Laidler PM, and Brzozowski T
- Subjects
- 5-Hydroxytryptophan metabolism, Administration, Oral, Animals, Biotransformation, Female, Indoleacetic Acids metabolism, Kynurenine metabolism, Male, Melatonin blood, Rats, Rats, Wistar, Serotonin metabolism, Tryptophan administration & dosage, Tryptophan blood, Chromatography, High Pressure Liquid, Gastrointestinal Tract metabolism, Melatonin metabolism, Spectrometry, Fluorescence, Spectrophotometry, Ultraviolet, Tryptophan metabolism
- Abstract
Melatonin is a major biosynthetic product of pineal gland exerting a potent antioxidant and the reactive oxygen metabolites scavenging activities but the mechanism of formation of this indole at extrapineal sources has not been fully elucidated. It is known that the gastrointestinal (GI)-tract plays an important role as a source of melatonin synthesis but the conversion of L-tryptophan into melatonin in the GI-tract of experimental animals and humans should be further examined. In this study, the conversion of L-tryptophan to melatonin was determined in the serum collected from rats administered intragastrically with this amino acid acting as melatonin precursor. For this purpose, a simple, sensitive and reliable method was developed for simultaneous determination of six L-tryptophan metabolites in rat serum, namely, 5-hydroxytryptamnie (5-HT), 5-hydroksytryptophan (5-HTR), kynurenin (KYN), antranilic acid (AA), indole-3-acetic acid (IAA) and melatonin that were analyzed in one chromatographic run by high-performance liquid chromatography (HPLC) with UV and native fluorimetric detection with multiple wavelengths. We used nucleosil Supelco C18 5 μm 4.6 mm x 250 nm column with the standard mobile phase consisting of solvent A (water/0.1% trifluoroacetic acid (TFA) and solvent B (methanol/0.1% TFA) in gradient elution. Fifty five rats received vehicle (saline) of L-tryptophan (50 mg/kg) or melatonin (50 mg/kg) by means of intragastric gavage and they were anesthetized and sacrificed at 0, 10, 20, 30, 60, 120 or 240 min upon L-tryptophan or melatonin administration for the venous blood withdrawal. The serum collected samples were kept on ice for the HPLC determination. The average recovery of 5-HT, 5-HRT, KYN, AA, TRP, IAA, and melatonin were 99±3%, 97±1.5%, 94±2.5%, 99±2.46, 98±1.5 and 98±2%, respectively. We conclude that 1) L-tryptophan is converted to melatonin in the GI-tract during the day when the pineal gland synthesis is inhibited, and 2) the reverse phase high performance liquid chromatography (RP-HPLC) is a new sensitive and reliable method that could be successfully applied to the study of kinetics and metabolism of L-tryptophan in GI-tract.
- Published
- 2012
16. RP-HPLC method for quantitative determination of cystathionine, cysteine and glutathione: An application for the study of the metabolism of cysteine in human brain.
- Author
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Bronowicka-Adamska P, Zagajewski J, Czubak J, and Wróbel M
- Subjects
- Brain Chemistry, Cystathionine gamma-Lyase metabolism, Humans, Brain metabolism, Chromatography, High Pressure Liquid methods, Chromatography, Reverse-Phase methods, Cystathionine analysis, Cysteine analysis, Glutathione analysis
- Abstract
The RP-HPLC method for a simultaneous separation and quantitation of the dinitrophenyl derivative of cystathionine (N,N'-di-DNP) in biological samples together with GSH, GSSG, cysteine and cystine, provides a very useful tool for investigation of the transsulfuration pathway in biological samples, at the same providing results which reflect the redox status (GSH/GSSG ratio) and the potential of the generation of H₂S. An application of the method for the study of the process of transsulfuration in various human brain regions shows the presence of cystathionine in all the investigated regions; it also demonstrates that cystathionine levels vary greatly between particular regions. The highest level in the thalamus and the lowest in the cerebellum were associated with respectively a low or high γ-cystathionase activity, and at the same time, a high cysteine and GSH level in the thalamus and a low value in the cerebellum. Based on the above results, one may suggest a regulatory mechanism responsible for inhibition of the CGL activity at high concentration values of cysteine and/or GSH. Simultaneous determinations of GSH and GSSG levels allow for determining the GSH/GSSG ratio, which reflects tissue redox status. The method may be also employed in determining the activity of γ-cystathionase and cystathionine-β synthase., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
17. The chemotactic activity of beta-carotene in endothelial cell progenitors and human umbilical vein endothelial cells: A microarray analysis.
- Author
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Polus A, Kiec-Wilk B, Hartwich J, Balwierz A, Stachura J, Dyduch G, Laidler P, Zagajewski J, Langman T, Schmitz G, Goralczyk R, Wertz K, Riss G, Keijer J, and Dembinska-Kiec A
- Abstract
Objectives: Endothelial cells and their progenitors play an important role in angiogenesis that is essential for organogenesis and tissue remodelling, as well as for inflammatory responses and carcinogenesis in all periods of life. In the present study, the authors concentrated on the direct effect of beta-carotene (BC) on human umbilical cord-originated endothelial progenitor cells and human umbilical vein endothelial cells., Methods: BC uptake was measured using high-performance liquid chromatography. The effect on cell proliferation was measured based on bromodeoxyuridine incorporation. Chemotaxis was performed in a Boyden chamber. The influence on tubular-like structure formation was investigated using a three-dimensional assay in Matrigel (Becton Dickinson, USA) both in an in vitro and in vivo model. Changes in gene expression were analyzed using the microarray hybridization method. Quantitative gene expression was estimated using the real-time polymerase chain reaction method., Results: It was shown that BC, in the physiological range of concentrations found in human blood, is a potent activator of chemotaxis of endothelial cells. Microarray data analysis revealed that the genes involved in cell-cell and cell-matrix adhesion, matrix reorganization and activation of chemotaxis were the most affected by BC genes in human umbilical vein endothelial cells and endothelial progenitor cells. These results were also confirmed in an in vivo angiogenesis model., Conclusion: BC, in the range of physiological concentrations, stimulates early steps of angiogenic activity of endothelial cells by activation of cellular migration, as well as by matrix reorganization and a decrease in cellular adhesion.
- Published
- 2006
18. Different effect of beta-carotene on proliferation of prostate cancer cells.
- Author
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Dulińska J, Gil D, Zagajewski J, Hartwich J, Bodzioch M, Dembińska-Kieć A, Langmann T, Schmitz G, and Laidler P
- Subjects
- Androgens, Apoptosis genetics, Blotting, Western, Cell Division genetics, Cell Line, Tumor drug effects, Dose-Response Relationship, Drug, Humans, Male, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Prostatic Neoplasms pathology, Receptors, Retinoic Acid genetics, Retinoic Acid Receptor alpha, Signal Transduction genetics, Gene Expression Regulation drug effects, Prostatic Neoplasms genetics, beta Carotene pharmacology
- Abstract
It was shown that high doses of beta-carotene (>30 microM) decrease proliferation of prostate cancer cells in vitro. However, it is rather doubtful whether such concentration of beta-carotene is really accessible at cellular level. We studied the effect of 3 and 10 microM beta-carotene on proliferation and gene expression in LNCaP and PC-3 prostate cancer cell lines. Beta-carotene--more efficiently absorbed from medium by androgen-sensitive LNCaP cells--increased proliferation of LNCaP cells whereas it had weaker effect on PC-3 cells. Initial global analysis of expression of genes in both cell lines treated with 10 microM beta-carotene (Affymetrix HG-U133A) showed remarkable differences in number of responsive genes. Their recognition allows for conclusion that differences between prostate cancer cell lines in response to beta-carotene treatment are due to various androgen sensitivities of LNCaP and PC-3 cells. Detailed analysis of expression of selected genes in beta-carotene treated LNCaP cells at the level of mRNA and protein indicated that the observed increase of proliferation could have been the result of slight induction of a few genes affecting proliferation (c-myc, c-jun) and apoptosis (bcl-2) with no significant effect on major cell cycle control genes (cdk2, RB, E2F-1).
- Published
- 2005
- Full Text
- View/download PDF
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