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Your search keyword '"Pulaski, Lukasz"' showing total 46 results
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46 results on '"Pulaski, Lukasz"'

5. Mesalazine–PAMAM Nanoparticles for Transporter-Independent Intracellular Drug Delivery: Cellular Uptake and Anti-Inflammatory Activity

Author

Gorzkiewicz,Michal, Marcinkowska,Monika, Studzian,Maciej, Karwaciak,Iwona, Pulaski,Lukasz, Klajnert-Maculewicz,Barbara, Gorzkiewicz,Michal, Marcinkowska,Monika, Studzian,Maciej, Karwaciak,Iwona, Pulaski,Lukasz, and Klajnert-Maculewicz,Barbara

Abstract

Michal Gorzkiewicz,1,2 Monika Marcinkowska,1 Maciej Studzian,3,4 Iwona Karwaciak,4,5 Lukasz Pulaski,3,4 Barbara Klajnert-Maculewicz1 1Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland; 2Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; 3Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland; 4Laboratory of Transcriptional Regulation, Institute of Medical Biology PAS, Lodz, Poland; 5Laboratory of Epigenetics, Institute of Medical Biology PAS, Lodz, PolandCorrespondence: Michal Gorzkiewicz, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, Lodz, 90-236, Poland, Tel +48 42 635 41 47, Email michal.gorzkiewicz@biol.uni.lodz.plBackground: Mesalazine is one of the main drugs used to treat inflammatory bowel diseases. However, its applicability is limited by its rapid inactivation and removal from the organism, as well as the need for its membrane transporter-dependent cellular uptake to exert therapeutic effect. The present study involved the development of an innovative nanocarrier, based on poly(amidoamine) (PAMAM) dendrimer of the 4th generation, to obtain higher concentrations of the drug in the intestinal epithelial cells, thus increasing its anti-inflammatory potential. The work involved synthesis and in vitro characterization of covalent PAMAM-mesalazine conjugate with succinic linker.Results: PAMAM-mesalazine conjugate was synthesized and characterized by 1H NMR, 13C NMR, FTIR and MALDI-TOF MS. This allowed to confirm the purity of the obtained compound and intermediates. Based on the analyses, it was found that ~45 drug molecules were successfully attached to one molecule of PAMAM dendrimer. The conjugate was then characterized in terms of hydrodynamic diameter, zeta potential, spectral pro

Published
2023

13. Analysis of the properties of the N-terminal nucleotide-binding domain of human P-glycoprotein

Author

Booth, Catherine L., Pulaski, Lukasz, Gottesman, Michael M., and Pastan, Ira

Subjects
Biochemistry -- Research, Nucleotides -- Research, Glycoproteins -- Research, Adenosine triphosphate -- Research, Magnesium -- Research, Biological sciences, Chemistry
Abstract

Research has been conducted on the human P-glycoprotein. The nature of the Mg (super)2+ -ATP binding in the N-terminal nucleotide binding domain of the human P-glycoprotein has been investigated.

Published
2000

27. Screening the Expression of ABCB6 in Erythrocytes Reveals an Unexpectedly High Frequency of Lan Mutations in Healthy Individuals

Author

Koszarska, Magdalena, primary, Kucsma, Nora, additional, Kiss, Katalin, additional, Varady, Gyorgy, additional, Gera, Melinda, additional, Antalffy, Geza, additional, Andrikovics, Hajnalka, additional, Tordai, Attila, additional, Studzian, Maciej, additional, Strapagiel, Dominik, additional, Pulaski, Lukasz, additional, Tani, Yoshihiko, additional, Sarkadi, Balazs, additional, and Szakacs, Gergely, additional

Published
2014
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28. Plants from the orchid family (Orchidaceae) in the Częstochowa Upland (south-central Poland)

Author

Pulaski, Lukasz and Uniwersytet Łódzki, K atedra Biofizyki Molekularnej

Abstract

In the 1992 and 1993 vegetation seasons, investigations were carried out on the distribution of plants from the orchid family in the area roughly corresponding to the Wyżyna Częstochowska (Częstochowa Upland) mesoregion (341.31 in the classification of Kondracki 1980). During those investigations, sites of occurrence were found for 22 species, 5 interspecific hybrids and 1 intergeneric hybrid. Of special interest are the sites of Russow’s Marsh Orchid (Dactybrhiza russowii), Violet Helleborine (Epipaclis purpurata) and Greater Butterfly Orchid (flatanihera chloraniha) as well as of aJl the nothotaxa, which have never been found in this area before. Zadanie pt. „Digitalizacja i udostępnienie w Cyfrowym Repozytorium Uniwersytetu Łódzkiego kolekcji czasopism naukowych wydawanych przez Uniwersytet Łódzki” nr 885/P-DUN/2014 dofinansowane zostało ze środków MNiSW w ramach działalności upowszechniającej naukę.

Published
2002

34. Phosphorylation of Smad7 at Ser-249 does not interfere with its inhibitory role in transforming growth factor-beta-dependent signaling but affects Smad7-dependent transcriptional activation

Author

Pulaski, Lukasz, Landström, Maréne, Heldin, Carl-Henrik, Souchelnytskyi, Serhiy, Pulaski, Lukasz, Landström, Maréne, Heldin, Carl-Henrik, and Souchelnytskyi, Serhiy

Abstract

Smad proteins are major components in the intracellular signaling pathway of transforming growth factor-beta (TGF-beta), and phosphorylation is an important mechanism in regulation of their functions. Smad7 was identified as a potent inhibitor of TGF-beta-dependent signaling. We have identified serine 249 in Smad7 as a major phosphorylation site, the phosphorylation of which was not affected by TGF-beta1. Abrogation of the phosphorylation by substitution of Ser-249 with alanine or aspartic acid residues did not affect the ability of Smad7 to inhibit TGF-beta1 and BMP7 signaling. No differences were found in the stability or in the intracellular distribution of Smad7 mutants compared with the wild-type molecule. However, Smad7 fused to the DNA-binding domain of GAL4 induced transcription from a reporter with mutated TATA minimal promoter in a Ser-249-dependent manner. Moreover, a reporter with the SV40 minimal promoter was inhibited by GAL4-Smad7, and this effect was also dependent on Ser-249 phosphorylation. The amplitude of effects on transcriptional regulation was dependent on cell type. Our results suggest that phosphorylation of Smad7, unlike phosphorylation of the receptor-regulated Smads, does not regulate TGF-beta signaling but rather affects TGF-beta-independent effects of Smad7 on transcriptional regulation.

Published
2001
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35. Activation of -catenin signalling by GSK-3 inhibition increases P-glycoprotein expression in brain endothelial cells

Author

Lim, Joseph C, primary, Kania, Katarzyna D, additional, Wijesuriya, Hasini, additional, Chawla, Sangeeta, additional, Sethi, Jaswinder K, additional, Pulaski, Lukasz, additional, Romero, Ignacio A, additional, Couraud, Pierre O, additional, Weksler, Babette B, additional, Hladky, Stephen B, additional, and Barrand, Margery A, additional

Published
2008
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44. Contribution of activated beta3 integrin in the PDI release from endothelial cells.

Author

Ponamarczuk H, Popielarski M, Stasiak M, Bednarek R, Studzian M, Pulaski L, Babinska A, and Swiatkowska M

Subjects
Actin Cytoskeleton metabolism, Cell Adhesion, Cell Line, Disulfides metabolism, Fibronectins metabolism, Humans, Hybridomas, Immunoblotting, Microscopy, Confocal, Polylysine metabolism, Endothelial Cells metabolism, Extracellular Space metabolism, Integrin beta3 metabolism, Protein Disulfide-Isomerases metabolism
Abstract

Protein disulfide isomerase (PDI) is an abundant reticulum endoplasmic protein but also acts as an important functional regulator of some extracellular surface proteins. Recent studies suggest that PDI plays a role in integrin activation and thrombus formation. The aim of this study was to examine whether activation of integrin is the first stage leading to release of PDI from the subcellular compartments of endothelial cells to extracellular space. Our results show that endothelial cells which adhere to fibronectin or fibrinogen release significantly more PDI than those which adhere to poly-L-lysine. Cells treated with RGD peptide, Src and FAK kinase inhibitors and anti alphaVbeta3 antibody display lower PDI secretion. The destruction of the actin cytoskeleton of endothelial cells by cytochalasin D inhibits PDI release. When the endothelial cells adhere to fibrinogen or fibronectin, PDI and alphaVbeta3 gain free thiol groups. Our data suggest that upon activation of integrins, PDI is released from endothelial cells and forms a disulfide bond complex with alphaVbeta3 integrin.

Published
2018
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45. Activation of beta-catenin signalling by GSK-3 inhibition increases p-glycoprotein expression in brain endothelial cells.

Author

Lim JC, Kania KD, Wijesuriya H, Chawla S, Sethi JK, Pulaski L, Romero IA, Couraud PO, Weksler BB, Hladky SB, and Barrand MA

Subjects
ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Animals, Blood-Brain Barrier drug effects, Blood-Brain Barrier metabolism, Blood-Brain Barrier physiology, Brain cytology, Brain drug effects, Cell Line, Transformed, Cells, Cultured, Down-Regulation drug effects, Down-Regulation physiology, Endothelial Cells cytology, Gene Expression Regulation drug effects, Glycogen Synthase Kinase 3 metabolism, Glycogen Synthase Kinase 3 beta, Humans, Indoles pharmacology, Male, Oximes pharmacology, Rats, Rats, Wistar, Signal Transduction drug effects, Up-Regulation drug effects, Up-Regulation physiology, beta Catenin genetics, ATP Binding Cassette Transporter, Subfamily B, Member 1 biosynthesis, Brain metabolism, Endothelial Cells metabolism, Gene Expression Regulation physiology, Glycogen Synthase Kinase 3 antagonists & inhibitors, Signal Transduction physiology, beta Catenin physiology
Abstract

This study investigates involvement of beta-catenin signalling in regulation of p-glycoprotein (p-gp) expression in endothelial cells derived from brain vasculature. Pharmacological interventions that enhance or that block beta-catenin signalling were applied to primary rat brain endothelial cells and to immortalized human brain endothelial cells, hCMEC/D3, nuclear translocation of beta-catenin being determined by immunocytochemistry and by western blot analysis to confirm effectiveness of the manipulations. Using the specific glycogen synthase kinase-3 (GSK-3) inhibitor 6-bromoindirubin-3'-oxime enhanced beta-catenin and increased p-gp expression including activating the MDR1 promoter. These increases were accompanied by increases in p-gp-mediated efflux capability as observed from alterations in intracellular fluorescent calcein accumulation detected by flow cytometry. Similar increases in p-gp expression were noted with other GSK-3 inhibitors, i.e. 1-azakenpaullone or LiCl. Application of Wnt agonist [2-amino-4-(3,4-(methylenedioxy) benzylamino)-6-(3-methoxyphenyl)pyrimidine] also enhanced beta-catenin and increased transcript and protein levels of p-gp. By contrast, down-regulating the pathway using Dickkopf-1 or quercetin decreased p-gp expression. Similar changes were observed with multidrug resistance protein 4 and breast cancer resistance protein, both known to be present at the blood-brain barrier. These results suggest that regulation of p-gp and other multidrug efflux transporters in brain vasculature can be influenced by beta-catenin signalling.

Published
2008
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46. Cytotoxicity, cytoprotection and neurotoxicity of novel deprenyl-related propargylamines, stable nitroxide free radicals, in vitro and in vivo.

Author

Namiecinski M, Pulaski L, Kochman A, Skolimowski J, Bartosz G, and Metodiewa D

Subjects
Animals, Antioxidants chemistry, Apoptosis drug effects, Cell Survival drug effects, Dopamine metabolism, Dose-Response Relationship, Drug, Female, Neurons metabolism, Neurons pathology, PC12 Cells drug effects, PC12 Cells pathology, Pargyline chemistry, Propylamines chemistry, Rats, Rats, Inbred BUF, Structure-Activity Relationship, Antioxidants toxicity, Neurons drug effects, Neuroprotective Agents toxicity, Nitrogen Oxides toxicity, Pargyline analogs & derivatives, Pargyline toxicity, Propylamines toxicity
Abstract

Since novel synthesized deprenyl-related derivatives of nitroxides, named "JSAKs", have been shown to possess antioxidative properties, their cytotoxicity on neuronal-like PC-12 cells line was examined. The antiproliferative effect of two selected JSAKs was examined and expressed as IC10, IC50 and IC90, and compared with those of the parent nitroxide (Nx-640), model nitroxide TEMPO and deprenyl. There were substantial differences in the dose-dependence of all the observed antiproliferative and cytotoxic effects. Compared to anticancer drugs and apoptosis inducers with topoisomerase inhibitor properties (etoposide and camptothecin), novel compounds displayed cytotoxicity at considerably higher concentrations. The dose-dependent anti-apoptotic potency of JSAKs and Nx-640 was also investigated and compared to TEMPO and deprenyl effects. The observed structure-dependent correlation was very encouraging and prompted us to screen and to compare the in vivo time-dependent effects of JSAKs, Nx-640 and deprenyl administration on the rat intact nigrostriatal neurocytes. TH-immunochemistry was applied as the test method and marker for the changes in the state of the rat catecholaminergic system, also giving evidence that low-toxic and cell-permeable JSAKs can cross the blood-brain barrier, which is the mandatory prerequisite for the therapeutic application of antioxidants and drugs to the brain. Taken together, it can be concluded with great certainty that novel deprenyl-related JSAKs might be especially good candidates for further anticancer investigations in vitro and in vivo and future pharmacological applications.

Published
2004

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