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Homocysteine, heat shock proteins, genistein and vitamins in ischemic stroke - pathogenic and therapeutic implications

100%
Banecka-Majkutewicz Z., Sawuła W., Kadziński L., Węgrzyn A., Banecki B.
Acta Biochimica Polonica
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2012
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vol. 59
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issue 4
495-499
EN
Stroke is one of the most devastating neurological conditions, with an approximate worldwide mortality of 5.5 million annually and loss of 44 million disability-adjusted life-years. The etiology of stroke is often unknown; it has been estimated that the etiology and pathophysiology remains unexplained in more than 40% of stroke cases. The conventional stroke risk factors, including hypertension, diabetes mellitus, smoking, and cardiac diseases, do not fully account for the risk of stroke, and stroke victims, especially young subjects, often do not have any of these factors. It is very likely that inflammation, specific genetic predispositions and traditional risk factors interact with each other and may together increase the risk of stroke. Inflammatory and immune responses play important roles in the course of ischemic stroke. Hyperhomocysteinemia (hcy) is considered a modifiable risk factor for stroke, possibly through an atherogenic and prothrombotic mechanism. Both genetic and environmental factors (e.g., dietary intake of folic acid and B vitamins) affect homocysteine level. Identification of the role of hcy as a modifiable risk factor for stroke and of HSPs as regulators of the immune response may lead to more effective prevention and treatment of stroke through dietary and pharmacological intervention. Dietary modification may also include supplementation with novel preventive compounds, such as the antioxidative isoflavones - genistein or daidzein.
2
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Comparison of siRNA-mediated silencing of glycosaminoglycan synthesis genes and enzyme replacement therapy for mucopolysaccharidosis in cell culture studies

86%
Chmielarz I., Gabig-Cimińska M., Malinowska M., Banecka-Majkutewicz Z., Węgrzyn A., Jakobkiewicz-Banecka J.
Acta Biochimica Polonica
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2012
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vol. 59
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issue 4
697-702
EN
Cytotoxicity of laronidase (Aldurazyme®), employed in enzyme replacement therapy (ERT) for mucopolysaccharidosis type I (MPS I) and various siRNAs, tested previously in studies on substrate reduction therapy (SRT) for mucopolysaccharidoses, was tested. The enzyme did not cause any cytotoxic effects, and the siRNAs did not inhibit growth of most investigated cell lines. However, some cytotoxic effects of some tested siRNAs were observed in one MPS IIIA cell line. The efficacy of a combination of enzyme replacement therapy and siRNA-based substrate deprivation therapy was tested on three MPS I cell lines. Surprisingly, different results were obtained for different cell lines. The decrease of glycosaminoglycan storage in cells treated simultaneously with both methods was: (i) less pronounced than obtained with either of those methods used alone in one cell line, (ii) similar to that observed for enzyme replacement therapy in another cell line, and (iii) stronger than that obtained with either of the methods used alone in the third cell line. Therefore, it appears that the effects of various therapeutic methods may strongly depend on the features of the MPS cell line.
3
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Increased levels of antibodies against heat shock proteins in stroke patients

86%
Banecka-Majkutewicz Z., Grabowski M., Kadziński L., Papkov A., Węgrzyn A., Banecki B.
Acta Biochimica Polonica
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2014
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vol. 61
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issue 2
379-383
EN
Ischemic stroke is the second leading cause of death worldwide. One of the main risk factors of the ischemic stroke is atherosclerosis which is a chronic inflammatory and immune-mediated disease. Bacterial infections generate specific human antibodies against various antigens, including Hsps. It has been demonstrated that Hsps are selectively overexpressed in the atherosclerotic lesions. The amino acid sequence homology between human and bacterial Hsps may lead to an autoimmune response by immunological cross-reaction. Such immune response against Hsps overexpressed in the blood vessels under stressful conditions may contribute to inflammatory processes and subsequent development of atherosclerosis. In this study we determined the antibody levels against bacterial and human Hsp by ELISA in blood plasma obtained from stroke patients. Using ANOVA we analyzed levels of Hsp-antibodies in control and patient groups and correlate them with several stroke risk factors. The group of stroke patients had elevated levels of anti-Hsp antibodies compared to the control group. We also discovered an antibody level increase in patients that previously underwent another stroke. Our data provide evidence that autoimmunity could underlie formation of atherosclerosis plaque leading to stroke.
4
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Role of heat-shock proteins and cobalamine in maintaining methionine synthase activity

86%
Grabowski M., Banasiuk R., Węgrzyn A., Kędzierska B., Lica J., Banecka-Majkutewicz Z., Banecki B.
Acta Biochimica Polonica
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2012
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vol. 59
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issue 4
489-493
EN
Atheromatous plaque is one of the most common cardiovascular-related diseases. Reports show a connection between its development and the levels of homocysteine. In pathological states high levels of homocysteine in the organism can be caused by the malfunction of the methionine synthase pathway. Bacterial methionine synthase (MetH) is a homologue of the human methionine syntase (MS). In this study we aimed to investigate the functional relations between MetH and its cofactor - cobalamine - under stress conditions. We have demonstrated that heat shock proteins (Hsp 70/100 system or HtpG) can protect MetH activity under stress conditions. Moreover, in the presence of cobalamine they can restore the activity of partially denatured methionine synthase.
5
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Improved HPLC method for total plasma homocysteine detection and quantification

86%
Sawuła W., Banecka-Majkutewicz Z., Kadziński L., Jakóbkiewicz-Banecka J., Węgrzyn G., Nyka W., Banecki B.
Acta Biochimica Polonica
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2008
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vol. 55
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issue 1
119-126
EN
Recent clinical research has pointed at hyperhomocysteinemia as an independent risk factor in a number of cardiovascular and neurological diseases. We have improved a chromatographic method of total plasma homocysteine measurements in order to obtain higher sensitivity, reliability and reproducibility. The method demonstrates excellent linearity (R = 0.999), range (< 2-100 µM), precision (instrumental RSD 0.06 and method RSD 1.17), accuracy (recovery of 99.92 and RSD 1.27), reproducibility, quantification limit and ruggedness (e.g. pH from 2.0 to 2.5). Because even a small increase in homocysteine level can be a significant risk factor of cardiovascular diseases, such a precise method is required. The constructed method allows the measurement of plasma pyridoxal phosphate, PLP, the co-enzyme form of vitamin B6, on the same column and similar reagents. The developed method has been successfully applied to measure both total plasma and serum homocysteine in a group of acute stroke patients.
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