Vol.7 No.4 December 2002

Volume 7 (2002) pp 961-969
Title ELECTRIC INTERACTIONS AT THE LIPID MEMBRANE SURFACE
Authors Marian Podolak* and Dariusz Man
Abstract This work presents the results of an experimental study and of computer simulations concerning electric interactions in the surface layer of egg yolk lecithin (EYL) liposome membranes. The surface layer is formed by EYL polar heads, which possess features of electric dipoles, and positive charged polar heads belonging to admixtures of quaternary ammonium salts (AS). The results of the experimental study are in good agreement with the ones of the computer simulations. It was found that fluidity of the membranes, at a given concentration of AS, obtains the extremal (minimal) value. Similarly, the binding energy of the dipoles-positive charges system behaves like that in computer simulations. Moreover, the locations of the fluidity extremum and those of the binding energy depend on the charge of the AS polar heads as well as on the degree of electric interactions screening by the environment. At a certain optimal value of the screening coefficient, the energy of the system is the lowest (the most negative) and together with the rise in AS charge, the minimum of the energy moves towards its higher concentrations.
Address and Contact Information Institute of Physics, Opole University, Oleska 48, 45-052 Opole, Poland
* Corresponding author, E-mail: podolak@uni.opole.pl
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 971-982
Title COMPUTER SIMULATION STUDIES ON THE SIGNIFICANCE OF LIPID POLAR HEAD CHARGE
Authors Krystian Kubica*
Abstract Ripple phase modelling was achievable by taking into consideration the dipole structure of the polar heads of model membrane molecules. Computer simulations enabled the selective analysis of a model membrane. Considering only the hydrophobic part of the lipid membrane, the gel-fluid transition stage can be obtained in such a simulation. Assuming an additional degree of freedom, the entire molecule can move along the normal to the membrane surface projected from two C-C bonds. The amounts of shifted lipids were 17% and 33% at temperatures of 300 K (gel) and 330 K (fluid), respectively. Taking into account only polar head interactions in media of different ionic strength I, dielectric constant e, and an effective charge and temperature, we could observe the same behaviour of the examined system independently of the values of I and e when the charge was reduced to q/2. The amount of shifted heads at 300 K decreases sharply with the reduced charge value, with an accompanying increase in the number of 'standing' polar heads. Summing up, it can be stated that hydrocarbon lipid chains exhibit a greater tendency to displacement in the fluid state than in the gel state. However, the polar heads behave in the opposite way: there are more displaced heads at 300 K than at 330 K. Thus, the overall analysis of the interactions between the molecules of the model membrane should enable us to find model parameters suitable for studying the lipid membrane at a wide range of temperatures. Finally, an electrostatic profile close to the membrane surface could be estimated in different membrane states. This should be useful in membrane-biologically active compound interaction analysis.
Address and Contact Information Department of Physics and Biophysics, Agricultural University, Norwida 25, 50-375 Wrocław, Poland
* E-mail:KUBICA@OZI.AR.WROC.PL
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 983 - 993
Title MECHANISTIC APPROACH TO MEMBRANE MASS TRANSPORT PROCESSES (MINI REVIEW)
Authors Marian Kargol
Abstract Since the physical interpretation of practical Kedem-Katchalsky equations is not clear, we consider an alternative, mechanistic approach to membrane transport generated by osmotic and hydraulic pressure. We study a porous membrane with randomly distributed pore sizes (radii). We postulate that the reflection coefficient (sp) of a single pore may equal 1 or 0 only. From this postulate we derive new (mechanistic) transport equations. Their advantage is in clear physical interpretation.
Address and Contact Information Institute of Physics, Świętokrzyska Academy, 25-406 Kielce, Poland
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 995-1018
Title ALTERATIONS IN CELL NUCLEI DURING APOPTOSIS
Authors Małgorzata Rogalińska
Abstract Apoptosis is a genetically programmed phenomenon that aids in maintaining homeostasis in multicellular organisms. The characteristic morphological features of apoptosis are highly conservative and are dependent on the cell type and the apoptotic inducer. The nuclear events occurring during apoptosis include changes at the molecular level (i.e. DNA cleavage, modifications of nuclear polypeptides, and proteolysis of several proteins important for cell maintenance), and, consequently, alterations at the morphological level (i.e. chromatin condensation, nuclear shrinkage, DNA fragmentation and apoptotic body formation). These events are still not fully understood. It is very probable that a progressive decrease in pH could also be an essential factor for the induction of nuclease and protease activities, and an important element of the optimal conditions for their function. This review details the current state of knowledge on apoptotic nuclear events, with particular focus on the proteins involved in the execution of apoptosis in cell nuclei, and on the differences in substrate cleavage profiles for different types of cell undergoing cell death.
Address and Contact Information University of Łódź, Department of Cytobiochemistry, Banacha 12/16, 90-237 Łódź, Poland
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1019-1035
Title THE NUCLEAR LAMINS AND THE NUCLEAR ENVELOPE
Authors Ryszard Rzepecki
Abstract The cell nucleus is separated from the rest of the cell by the nuclear envelope. The nuclear envelope, nuclear envelope proteins and nuclear lamina organise the structure of the entire nucleus and the chromatin via a myriad of interactions. These interactions are dynamic, change with the change (progress) of the cell cycle, with cell differentiation and with changes in cell physiology.
Address and Contact Information Institute of Biochemistry and Molecular Biology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wrocław, Poland
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1037-1045
Title THE ISOFORM- AND LOCATION-DEPENDENCE OF THE FUNCTIONING OF THE PLASMA MEMBRANE CALCIUM PUMP
Authors Ludmiła Żylińska, Iwona Kawecka, Lilla Lachowicz and Janusz Szemraj
Abstract The plasma membrane is a specialised multi-component structure with inter- and intracellular signalling functions. Ca2+ plays a crucial role in cellular physiology, and an ATP-driven plasma membrane calcium pump (PMCA) plays the greatest role in the maintenance of a low free Ca2+ concentration in the cytoplasm. The enzyme is coded by four separate genes (PMCA 1-4), and, due to alternative splicing, more than 20 variants can exist. PMCA 1 and 4 isoforms are present in almost all tissues, whereas PMCA 2 and 3 are found in more specialised cell types. The variants differ primarily in their regulatory regions, thus the modulation of calcium pump activity strongly depends on the isoform and the membrane composition. The unique function of PMCA isoforms was confirmed using the practical experimental models-a rat pheochromocytoma cell line, a human neuroblastoma cell line, or, more recently, knockout mice. In addition, based on the finding that PMCA could interact with several specific signaling proteins, it was concluded that its location in defined sites of the cell membrane could be a prerequisite for efficient intercellular communication.
Address and Contact Information Neurochemical Laboratory, Department of Biochemistry, Medical University, Mazowiecka 6/8, 92-215 Łódź, Poland
* Corresponding author, E-mail: luska@csk.am.lodz.pl
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1047-1057
Title THE ROLE OF FOCAL ADHESION KINASE IN THE EMIGRATION OF CELLS FROM CONFLUENT CULTURES
Authors Halina Trembacz1, Joanna Miłoszewska1, Bożena Szaniawska1, Maciej Małecki1*, Małgorzata Przybyszewska1, Tomasz Skorski2 and Przemysław Janik1**
Abstract We studied the effect of the modification of focal adhesion kinase (FAK) on the growth, migration and adhesion of C3H 10T1/2 cells. Cells transfected with plasmid coding for antisense FAK displayed a low level of FAK protein. Interestingly, the transfected cells achieved a higher saturation density at confluence, and displayed reduced adhesion and enhanced emigration from a confluent layer of cells when stimulated with fibronectin. In conclusion, it can be postulated that FAK plays an important role in the mechanism of contact inhibition.
Address and Contact Information 1Department of Cell Biology, Cancer Center, M. Skłodowska-Curie Institute of Oncology, W.K. Roentgen 5, 02-781 Warsaw, Poland,
2Center for Biotechnology, Temple University, 1900 N 12th Street, Philadelphia, USA
*Scholar of the Foundation For Polish Science 2002
** Corresponding author, E-mail: pjanik@coi.waw.pl
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1059-1064
Title EFFECT OF INTRAMUSCULAR APPLICATION OF SELECTED NEUROPEPTIDES ON MORPHOLOGY OF MUSCLE
Authors Hanna Gendek-Kubiak
Abstract The aim of the study was to examine a morphological picture of guinea pig skeletal muscles injected with neuropeptide Y (NPY), substance P (SP) or vasoactive intestinal peptide (VIP), to evaluate the influence of a single injection of the mentioned neuropeptides (NPS) on muscle morphology and mast cell, T lymphocyte and macrophage chemotaxis. There were different degrees of muscle fibre injuries as well as different intensities and compositions of infiltrations inside the muscle after the introduction of the NPS. The observed changes did not disappear, but increased after 24 hours, comparing to the 3-hour post-injection changes, suggesting that NPS are proinflammatory rather than antiinflammatory factors in skeletal muscles. The local, particularly delayed action of NPS in vivo requires further studies.
Address and Contact Information Department of Cytophysiology, Histology and Embryology, Medical University of Łódź, ul. Narutowicza 60, 90-136 Łódź, Poland
E-mail: h_kubiak@hotmail.com
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1065 - 1071
Title REACTIVE OXYGEN SPECIES UPREGULATE EXPRESSION OF PAI-1 IN ENDOTHELIAL CELLS
Authors Maria Świątkowska1*, Janusz Szemraj2, Halid N.I. Al-Nedawi3 and Zofia Pawłowska1
Abstract Second messengers involved in the signal transduction pathway leading to induction of the plasminogen activator inhibitor (PAI-1) have not yet been well characterized. This study focuses on the mechanisms of regulation of PAI-1 expression by reactive oxygen species (ROS) in human endothelial cells. Inhibition of the tumor necrosis factor a (TNFa)-induced expression of PAI-1 by antioxidant N-acetyl-L-cysteine (NAC) indicated redox-sensitive mechanisms involved in the signalling pathway. Because TNFa induces PAI-1 production in endothelial cells, and NAC attenuated this response, we attempted to investigate the possible involvement of ROS in the activation of PAI-1 by TNFa. Upregulation of PAI-1 expression in endothelial cells by the stimulation with TNFa (50ng/ml) or H2O2 (10-200mM), observed by measurement of the antigen and mRNA levels, was reversed in the presence of NAC (20mM). The stimulatory effect of ROS was detected also at the level of the PAI-1 promoter in endothelial cells transfected with plasmid p800 LUC containing a PAI-1 promoter fragment (+71 to -800). The PAI-1 promoter activity was increased in the presence of ROS, and was suppressed by up to 75% in the presence of antioxidants [1]. On the basis of this study we can conclude that reactive oxygen species play an important role in a cytokine-induced activation of PAI-1 expression, and may act as a signal transduction messenger.
Address and Contact Information 1Department of Molecular and Medical Biophysics, 2Department of Biochemistry, Medical University of Łódź,
3Department of Biogenic Amines, PAS, Łódź, Poland
* Corresponding author, E-mail: swiatm@zdn.am.lodz.pl
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1073-1080
Title DYNAMIN: CHARACTERISTICS, MECHANISM OF ACTION AND FUNCTION
Authors Jolanta Wiejak and Elżbieta Wyroba
Abstract Dynamin - a member of the GTP-ase protein family - is essential for many intracellular membrane trafficking events in multiple endocytic processes. The unique biochemical features of dynamin - especially its propensity to assemble - enable severing the nascent vesicles from the membrane. The mechanism of dynamin's action is still a subject of debate - whether it functions as a mechanochemical enzyme or a regulatory GTPase. The GTPase domain of dynamin contains three GTP-binding motifs. This domain is very conservative across the species, including that recently cloned by us in the unicellular eukaryote Paramecium. Dynamin interacts with a number of partners such as endophilin and proteins involved in coordination of endocytosis with motor molecules. A growing body of evidence indicates that dynamin and dynamin-related proteins are involved both in pathology and protection against human diseases. The most interesting are dynamin-like Mx proteins exhibiting antiviral activity.
Address and Contact Information Nencki Institute of Experimental Biology, Pasteura 3, 02-093 Warszawa, Poland
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1081-1086
Title THIORIDAZINE INDUCES ERYTHROCYTE STOMATOCYTOSIS DUE TO INTERACTIONS WITH NEGATIVELY CHARGED LIPIDS
Authors Andrzej B. Hendrich, Katarzyna Lichacz, Anna Burek and Krystyna Michalak
Abstract Despite the fact that thioridazine is used clinically as a neuroleptic drug, little is known about the molecular mechanisms underlying its biological effects, in particular about its interactions with membranes. In the present work we investigate the influence of thioridazine on model and cell membranes, using calorimetry, DPH fluorescence polarization measurements, studies of haemolysis and scanning electron microscopy. The experiments show that thioridazine interacts with lipid bilayers and intercalates into bilayer structure. We found that erythrocyte stomatocytosis induced by the drug might be related to preferential interaction of thioridazine with charged lipids.
Address and Contact Information Department of Biophysics, Wrocław Medical University, Chałubińskiego 10, 50-368 Wrocław, Poland
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1087-1094
Title THE INTERACTION OF TRYPTOPHAN AND ANS WITH PAMAM DENDRIMERS
Authors Barbara Klajnert and Maria Bryszewska*
Abstract Dendrimers are globular, hyperbranched polymers possessing a high concentration of surface functional groups and internal cavities. These unique features make them very useful in many biomedical applications, especially as carrier molecules. In this study, the interaction of tryptophan and 1- anilinonaphthalene-8-sulfonic acid with three types of polyamidoamine dendrimers was examined. It was observed that the type of dendrimer surface group has a strong impact on the interactions between the dendrimers and fluorescent molecules.
Address and Contact Information Department of General Biophysics, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland
* Corresponding author, E-mail: marbrys@biol.uni.lodz.pl
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1095-1109
Title THE INFLUENCE OF MEMBRANE LIPID METABOLITES ON LYMPHOCYTE POTASSIUM CHANNEL ACTIVITY
Authors Andrzej Teisseyre1, Krystyna Michalak1 and Małgorzata Kuliszkiewicz-Janus2
Abstract In the present study, the whole-cell patch-clamp technique was applied to elucidate modulatory effects of high-density lipoproteins (HDL), sphingosine (SPH), sphingosine-1-phosphate (SPP), lysophosphatidic acid (LPA) and sphingosyl- phosphorylcholine (SPC) on the activity of Kv1.3 channels in human T lymphocytes (TL). Obtained data provide evidence that application of SPC at micromolar concentrations shifts the channel activation midpoint by about 20 mV towards positive membrane potentials. This effect occurs in a concentration-dependent manner and is saturated at SPC concentrations higher than 10 mM. The shift of channel activation midpoint is accompanied by a pronounced slowing of the activation kinetics. The modulatory effect of SPC is clearly voltage-dependent, being most potent at –20 mV and least potent at +60 mV. The steady-state inactivation curve is also shifted by about 20 mV towards positive membrane potentials. The kinetics of channel inactivation and deactivation (closure) remain unaffected upon SPC treatment. In contrast, application of HDL (250 mg/ml), SPH (50 and 100 mM), SPP (10 mM) and LPA (10 and 36 mM) does not exert any modulatory effect on the channel activity. The effect of SPC on Kv1.3 channel gating resembles the effect exerted by extracellular zinc at the concentration of 10 mM. It is concluded that the effect of SPC is specific and may be due to the presence of a choline residue in SPC molecules. The possible mechanism and the physiological significance of this modulatory effect on Kv1.3 channels are discussed.
Address and Contact Information 1Department of Biophysics, Wrocław Medical University, Chałubińskiego 10, 50-368 Wrocław, Poland,
2Department and Clinic of Haematology and Oncology, Wrocław Medical University, Pasteura 4, 50-367 Wrocław, Poland
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1111-1120
Title THE EFFECTS OF GROWTH REGULATORS ON SOMACLONAL VARIATION IN RYE (Secale cereale L.) AND SELECTION OF SOMACLONAL VARIANTS WITH INCREASED AGRONOMIC TRAITS
Authors Monika Rakoczy-Trojanowska
Abstract The aim of this research was to characterize somaclonal variation in populations derived from embryos cultured on two types of induction medium (supplemented with either 2,4-D or dicamba), as well as to select and characterize several somaclonal lines.. The sexual progenies of 40 R0 regenerants - A somaclones (derived on the medium with 2,4-D) and B somaclones (derived on the medium with dicamba) - were analysed according to the following traits: plant height, total number of tillers, number of productive tillers, spike length, number of spikelets per spike, spike compactness, number of normally developed grains per spike, weight of grains per spike, and the weight of 1000 grains. The results for twenty-two R1 plants surpassed the variability range for the control. The transmission of positive changes to the next generation was proved in the case of 8 originally chosen R1 plants: 7 plants selected from the A somaclones and one plant from the B somaclones. Five out of the eight created somaclonal lines proved to be stable somaclonal variants. The absolute rate of the efficiency of positive somaclonal changes was calculated as 0.64%.
Address and Contact Information Department of Plant Genetics, Breeding and Biotechnology, Warsaw Agricultural University, Nowoursynowska 166, 02-787 Warszawa, Poland
* E-mail: RAKOCZY@ALPHA.SGGW.WAW.PL
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1121-1129
Title LYSOSOMOTROPIC N,N- DIMETHYL a-AMINOACID n-ALKYL ESTERS AND THEIR QUATERNARY AMMONIUM SALTS AS PLASMA MEMBRANE AND MITOCHONDRIAL ATPases INHIBITORS
Authors Ewa Obłąk1, Tadeusz M. Lachowicz2, Jacek Łuczyński3 and Stanisław Witek3
Abstract A set of n-alkyl esters of N,N-dimethylglycine (DMG-n) and their methobromides (DMGM-n) was synthesized, and their activities on yeast Saccharomyces cerevisiae were compared. The compounds differ in the number of carbon atoms in the aliphatic chain. Aminoesters with 12 carbon atoms appeared to be most active. Unlike quaternary ammonium salts previously tested, the activities of the compounds were not pH-dependent; the minimal inhibitory concentrations (MIC) were identical at pH 8 and at pH 6. In contrast to quaternary ammonium salts, aminoesters showed similar effects on respiratory sufficient (rho+) and respiratory deficient (rhoo) mutants. When tested on glucose stimulated proton extrusion, aminoesters applied at MIC increased external pH. Aminoesters inhibited the plasma membrane H+-ATPase, whereas they were less inhibitory on the mitochondrial ATPase. In order to further compare the aminoesters and their corresponding quaternary ammonium salts, derivatives of N,N-dimethylalanine (DMAL-n and DMALMn, respectively) were synthesized. The quaternary ammonium salts appeared to have a higher inhibitory potency than aminoesters, especially at pH 8, and alanine derivatives inhibited growth at a lower concentration than glycine derivatives. Both alanine derivatives of the aminoester and the quaternary ammonium salt inhibited the plasma membrane H+- ATPase at lower concentrations than glycine derivatives, but the alanine aminoester was without a detectable effect on the mitochondrial ATPase.
Address and Contact Information 1Institute of Microbiology, University of Wrocław, Przybyszewskiego 65/73, 51-148 Wrocław, Poland,
2Institute of Biotechnology and Environmental Protection, University of Zielona Góra, Monte Cassino 3a, 65-561 Zielona Góra, Poland,
3Department of Chemistry, Technical University of Wrocław, 51-148 Wrocław, Poland
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1131-1136
Title THE ADJUVANT ACTIVITY OF LACTOFERRIN IN THE GENERATION OF DTH TO OVALBUMIN CAN BE INHIBITED BY BOVINE SERUM ALBUMIN BEARING α-D-MANNOPYRANOSYL RESIDUES
Authors Maja Kocięba1, Michał‚ Zimecki1, Marian Kruzel2 and Jeffrey Actor2
Abstract Lactoferrin (LF) is an iron-binding glycoprotein present in the cytoplasmic granules of neutrophils and in external secretions of mammals. Although the biological role of human and bovine lactoferrin has been extensively studied, there is still uncertainty as to the nature and function of lactoferrin receptors. We recently determined that methyl-α-D-mannopyranoside given intraperitoneally (i.p.) could suppress the adjuvant activity of LF in the generation of delayed-type hypersensitivity (DTH) to ovalbumin (OVA). We concluded that the lactoferrin effects in DTH are mediated by carbohydraterecognizing receptors like the mannose receptor (MR). This study indicates that subcutaneous (s.c.) administration of very small doses of the Man-bovine serum albumin (Man-BSA) complex, together with a sensitizing dose of the antigen, gives the same effects as i.p. administration of methyl-α-D-mannopyranoside. The latter is also a blocker of MR, although of a much lower affinity to the receptor than Man-BSA. The blocking of the adjuvant effect of LF by the Man- BSA complex (when given together with the sensitising dose of antigen) suggests that the function of antigen-presenting cells in the skin (presumably immature dendritic cells expressing MR) is inhibited. The results of our study indicate that a receptor with an affinity for mannose is essential for the mediation of adjuvant lactoferrin function in the generation of DTH.
Address and Contact Information 1Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland,
2University of Texas, Houston Health Science Center at Huston, MSB 4.506, 6431 Fannin Street, Houston, TX 77030, USA
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1137-1151
Title THE ROLE OF CELL WALL IN PLANT EMBRYOGENESIS
Authors Robert Malinowski* and Marcin Filipecki
Abstract This review presents recent data about cell wall involvement in plant embryogenesis. During plant development, the cell wall is subjected to precise regulation. During this process a bidirectional information exchange between the cell wall and the protoplast is observed. The cell wall also mediates in the cellcell (apoplastic) and cell to cell (symplastic) information flow. Especially some products derived from the hydrolysis of specific cell wall compounds can act as short distance signal transduction molecules during the development. Oligosaccharins are a group of such products. Their activity and sources focused the researchers' attention on the biochemical composition of the cell wall and the activity of some cell wall enzymes. The dramatic influence on the embryo body shape has also the cell wall synthesis machinery, including vesicular secretion pathways. Moreover, the interplay between the turgor pressure and counteracting cell walls and neighbouring cells (in higher organisms) creates the specific mechanical forces influencing the development of the whole plant. We conclude that discovering factors which can influence cell wall physiology and architecture is crucial for a better understanding of plant embryogenesis. In this review we summarize some recent experimental data reporting plant cell wall involvement in embryogenesis, putting special emphasis on somatic embryogenesis.
Address and Contact Information Department of Plant Genetics, Breeding and Biotechnology, Warsaw Agricultural University, Poland
* Corresponding author, E-mail: Syrop@netscape.net
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1153-1157
Title NATRIURETIC PEPTIDES REDUCE PLASMINOGEN ACTIVATOR INHIBITOR-1 EXPRESSION IN HUMAN ENDOTHELIAL CELLS
Authors Zofia Pawłowska1*, Hanna Jerczyńska1, Janusz Szemraj2, Patrycja Barańska1, Maria Świątkowska1 and Czesław S. Cierniewski1
Abstract Plasma concentrations of natriuretic peptides increase in some pathological conditions, but very little is known about the effect of these vasodilator peptides on the regulation of the blood coagulation system. The fundamental role in the regulation of fibrinolysis is played by plasminogen activator inhibitor type 1 (PAI-1). Recent studies demonstrate that natriuretic peptides can modulate PAI-1 expression in bovine aortic smooth muscle cells and rat aortic endothelial cells. In this report, we tested the effect of natriuretic peptides on PAI-1 expression in the human endothelial cell line (EA.hy 926). For this purpose, we treated the cell cultures with ANP, BNP and CNP, and modulation of PAI-1 synthesis was evaluated. We compared the effect of natriuretic peptides on synthesis and release of PAI-1 in unstimulated cells, and after activation with tumour necrosis factor a (TNFa). Natriuretic peptides abolished TNFa- induced upregulation of PAI-1 expression at both the PAI-1 mRNA and the antigen levels. The inhibitory efficiency was higher in the case of CNP when compared to that produced by ANP and BNP, particularly when TNFa-stimulated cells were used. We observed an inhibition of stimulatory effect of TNFa on PAI-1 expression also at the level of the PAI-1 promoter in cells transfected with a PAI-1 promoter fragment (+71 to -800) [1]. The PAI-1 promoter activity was markedly inhibited by C-type natriuretic peptide, already at a very low (0.001 mM) concentration of the peptide.
Address and Contact Information 1Department of Molecular and Medical Biophysics,
2Department of Biochemistry, Medical University of Łódź, Poland
* Corresponding author, E-mail: pawlow@zdn.am.lodz.pl
Pdf Document[Rozmiar: 1332 bajtĂłw]

Volume 7 (2002) pp 1158
Title Erratum
Pdf Document[Rozmiar: 1332 bajtĂłw]