Wyniki wyszukiwania - Biblioteka Nauki

1

Further evidence for the importance of lipid bilayers in the interaction between lactate dehydrogenase and phosphatidylserine

100%

Terlecki G. , Gutowicz J.

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tom 07

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nr 3

EN

Lactate dehydrogenase (LDH) is one of the glycolytic enzymes, which have been proved to have the capability to reverse non-specific adsorption on cellular membranous structures in vitro, as well as on the structural proteins of the contractile system of muscle cells. It has been suggested that this binding may play a physiological role, as it alters the enzyme’s kinetic properties. Our previous studies on this enzyme showed that its interaction with some anionic phospholipids reveals similar characteristics and similar effect on the activity of the enzyme to those wich had been observed for the interaction with membranous structures. Disruption of the lipid bilayers by nonionic detergent (Tween 20) restored the enzyme activity inhibited by the presence of phosphatidylserine (PS) liposomes. In this study, we used the measurement of enzyme tryptophanyl fluorescence spectra to monitor the interaction and possible changes in the enzyme conformation. The investigation provided further evidence of the importance of the bilayer structure in this interaction. Similarly to the effect on the activity of the enzyme, the addition of Tween 20 diminishes the quenching of the LDH tryptophanyl ﬂuorescence, and finally completely restores the fluorescence.

2

The association of glycolytic enzymes with cellular and model membranes

100%

Gutowicz J. , Terlecki G.

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nr Suppl.

3

Role of the lipid bilayer charge density in the interaction of lactate dehydrogenase with the bilayer

80%

Rogozik K. , Terlecki G. , Czapinska E. , Gutowicz J.

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nr Supplement 1

4

The influence of phospholipid on the kinetics of bovine heart muscle pyruvate kinase

80%

Dabrowska A. , Terlecki G. , Siemieniewski H.

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nr 2

5

Studies on the interaction of pig heart lactate dehydrogenase (LDH) with anionic phospholipids at low pH conditions; comparison with a muscle form of the enzyme

80%

Rogozik K. , Czapinska E. , Terlecki G.

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tom 53

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nr Supplement 1

6

The role of lipid phase structure in the interaction of lactate dehydrogenase with phosphatidylserine. Activity studies

80%

Terlecki G. , Czapinska E. , Gutowicz J.

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tom 07

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nr 3

EN

Lactate dehydrogenase is one of the enzymes of the glycolytic path. It has been shown to be able to bind in vitro to cellular membranes. The presence of anionic phospholipids induces changes in the catalytic properties of the enzyme similar to those found when the enzyme is bound to natural membranes. In this study, a nonionic detergent (Tween 20), at concentrations not affecting the catalytic activity of LDH, was used to study the role of the lipid supra-molecular structure in the interaction between pig skeletal muscle lactate dehydrogenase and phosphatidylserine. Tween 20 changes the equilibrium of concentrations between the lipid supra-molecular forms. The detergent at the used concentration values did not alter the activity of the enzyme when it was used on its own, but did diminish the level of inhibition induced by the studied phospholipid. The obtained results showed that the interaction is reversible and that the bilayer structure of the lipid is essential for the inhibition.

7

Matrix metalloproteinase-3 induction following photodynamic therapy with liposomal formulations of aminolevulinic acid and its methyl ester

51%

Jurczyszyn K. , Czapińska E. , Gamian E. , Hotowy K. , Terlecki G. , Symonowicz K. , Osiecka B. , Bronowicz A. , Ziółkowski P.

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2010

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tom Vol. 16, nr 2

182-186

EN

Photodynamic therapy (PDT) showed promising results in treatment of malignant and non-malignant disorders. The PDT requires for a therapeutic effect the combined action of photosensitizer and light. PDT causes direct cytotoxicity to malignant cells and may also have both direct and indirect effects upon various non-malignant components of tumor microenvironment. Unfortunately, some photosensitizers reveal low selectivity in pathologic tissues. Previous studies indicated that aminolevulinic acid (ALA) and its methyl ester (metvix) encapsulated in liposomes improved the quality and optimized results of PDT. Matrix metalloproteinases (MMPs) are enzymes implicated in various diseases by enabling the spread of disease. MMP-3 in turn, exerts the protective role in the development of tumors. We report the effect of liposomal formulation of ALA and metvix-based photodynamic therapy on induction of matrix metalloproteinase 3 in animal tumor model. Our results showed strong expression of MMP-3 in tumor-bearing rat tumor cells after PDT with liposomal formulations. The expression of MMP-3 in all tumor-bearing rats treated with PDT was stronger than those observed in animals free of tumors and especially in those treated with free precursor-PDT. The effect of liposomes was found to be important and these formulations elicited stronger intensity of immunohistochemical reactions than ALA- or metvix –PDT without liposomes.

PL

Terapia fotodynamiczna (photodynamic therapy – PDT) daje obiecujące wyniki w leczeniu złośliwych i niezłośliwych chorób. PDT wymaga połączonego działania fotouczulacza i światła dla uzyskania efektu terapeutycznego. PDT wywołuje efekt cytotoksyczny w patologicznych komórkach. Może także działać bezpośrednio i pośrednio na różne składniki mikrośrodowiska nowotworu. Niestety, niektóre fotouczulacze mają niską selektywność w tkankach chorobowych. Poprzednie badania wykazały, że kwas aminolewulinowy (ALA) i jego ester metylowy (metvix) umieszczone w liposomach poprawiały jakość i wyniki PDT. Metaloproteinazy macierzy (MMPs) są enzymami wprzęgniętymi w różne choroby umożliwiającymi ich szerzenie się. Z kolei MMP-3 odgrywa rolę ochronną w rozwoju nowotworów. W pracy przedstawiono wpływ działania preparatów liposomowych ALA i metviksu w warunkach PDT na indukcję MMP-3 w zwierzęcym modelu nowotworowym. Uzyskane wyniki wskazują na silną ekspresję MMP- 3 w komórkach nowotworu po PDT z użyciem preparatów liposomowych. Ekspresja MMP-3 u wszystkich zwierząt zaszczepionych nowotworem i traktowanych PDT była silniejsza niż u zwierząt wolnych od nowotworu i szczególnie od tych leczonych PDT z użyciem wolnych prekursorów. Wpływ liposomów okazał się być istotny i przyczyniał się do silniejszej reakcji immunohistochemicznej niż PDT bez tych nośników.

8

In vitro and in vivo matrix metalloproteinase expression after photodynamic therapy with a liposomal formulation of aminolevulinic acid and its methyl ester

41%

Osiecka B. , Jurczyszyn K. , Symonowicz K. , Bronowicz A. , Ostasiewicz P. , Czapinska E. , Hotowy K. , Krzystek-Korpacka M. , Gebarowska E. , Izykowska I. , Dziegiel P. , Terlecki G. , Ziolkowski P.

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nr 4

EN

Photodynamic therapy (PDT) is a well-known method for the treatment of malignant tumors, and its principles have been well established over the past 30 years. This therapy involves the application of a chemical called a photosensitizer and its subsequent excitation with light at the appropriate wavelength and energy. Topical photodynamic therapy with aminolevulinic acid (5-ALA) is an alternative therapy for many malignant processes, including nonmelanoma skin cancers such as basal-cell carcinoma (BCC). Our novel approach for this study was to use a liposomal formulation of 5-ALA and its methyl ester (commercially available as metvix) both in vitro and in vivo, and to check whether the liposome-entrapped precursors of photosensitizers can induce the expression of metalloproteinases (MMPs) in animal tumor cells and in other tissues from tumor-bearing rats and in selected cell lines in vitro. We also checked whether the application of tissue inhibitors of matrix metalloproteinases (TIMPs) has any effect on MMPs in the above-mentioned experimental models, and if they can cause complete inhibition of MMP expression. Immunohistochemical studies revealed that after the PDT, the intensity of expression of MMPs in healthy animals was very low and seen in single cells only. After the PDT in tumor-bearing rats, MMP-3 was expressed in the tumor cells with the highest intensity of staining in the tissues directly adjacent to the tumors, while MMP-2 and -9 were not found. In the control groups, there was no observed expression of MMPs. In vitro studies showed that MMP-3 was expressed in MCF-7 cells after PDT, but MMP-9 was not observed and MMP-2 was only seen in single cases. Our studies confirmed that the application of an MMP-3 inhibitor may block an induction of MMP-3 expression which had previously been initiated by PDT. The preliminary data obtained from cancer patients revealed that new precursors are effective in terms of PDT, and that using MMP inhibitors should be considered as a potential enhancing factor in clinical PDT.