The Experts below are selected from a list of 51 Experts worldwide ranked by ideXlab platform
Ilia V. Baskakov - One of the best experts on this subject based on the ideXlab platform.
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Preserving prion Strain identity upon replication of prions in vitro using recombinant prion protein
Acta Neuropathologica Communications, 2018Co-Authors: Natallia Makarava, Regina Savtchenko, Peter Lasch, Michael Beekes, Ilia V. BaskakovAbstract:Last decade witnessed an enormous progress in generating authentic infectious prions or PrP^Sc in vitro using recombinant prion protein (rPrP). Previous work established that rPrP that lacks posttranslational modification is able to support replication of highly infectious PrP^Sc with assistance of cofactors of polyanionic nature and/or lipids. Unexpectedly, previous studies also revealed that seeding of rPrP by brain-derived PrP^Sc gave rise to new prion Strains with new disease phenotypes documenting loss of a Strain identity upon replication in rPrP substrate. Up to now, it remains unclear whether prion Strain identity can be preserved upon replication in rPrP. The current study reports that faithful replication of Hamster Strain SSLOW could be achieved in vitro using rPrP as a substrate. We found that a mixture of phosphatidylethanolamine (PE) and synthetic nucleic acid polyA was sufficient for stable replication of Hamster brain-derived SSLOW PrP^Sc in serial Protein Misfolding Cyclic Amplification (sPMCA) that uses Hamster rPrP as a substrate. The disease phenotype generated in Hamsters upon transmission of recombinant PrP^Sc produced in vitro was strikingly similar to the original SSLOW diseases phenotype with respect to the incubation time to disease, as well as clinical, neuropathological and biochemical features. Infrared microspectroscopy (IR-MSP) indicated that PrP^Sc produced in animals upon transmission of recombinant PrP^Sc is structurally similar if not identical to the original SSLOW PrP^Sc. The current study is the first to demonstrate that rPrP can support replication of brain-derived PrP^Sc while preserving its Strain identity. In addition, the current work is the first to document that successful propagation of a Hamster Strain could be achieved in vitro using Hamster rPrP.
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Prion replication environment defines the fate of prion Strain adaptation.
Public Library of Science (PLoS), 2018Co-Authors: Elizaveta Katorcha, Natallia Makarava, Nuria Gonzalez-montalban, Gabor G Kovacs, Ilia V. BaskakovAbstract:The main risk of emergence of prion diseases in humans is associated with a cross-species transmission of prions of zoonotic origin. Prion transmission between species is regulated by a species barrier. Successful cross-species transmission is often accompanied by Strain adaptation and result in stable changes of Strain-specific disease phenotype. Amino acid sequences of host PrPC and donor PrPSc as well as Strain-specific structure of PrPSc are believed to be the main factors that control species barrier and Strain adaptation. Yet, despite our knowledge of the primary structures of mammalian prions, predicting the fate of prion Strain adaptation is very difficult if possible at all. The current study asked the question whether changes in cofactor environment affect the fate of prions adaptation. To address this question, Hamster Strain 263K was propagated under normal or RNA-depleted conditions using serial Protein Misfolding Cyclic Amplification (PMCA) conducted first in mouse and then Hamster substrates. We found that 263K propagated under normal conditions in mouse and then Hamster substrates induced the disease phenotype similar to the original 263K. Surprisingly, 263K that propagated first in RNA-depleted mouse substrate and then normal Hamster substrate produced a new disease phenotype upon serial transmission. Moreover, 263K that propagated in RNA-depleted mouse and then RNA-depleted Hamster substrates failed to induce clinical diseases for three serial passages despite a gradual increase of PrPSc in animals. To summarize, depletion of RNA in prion replication reactions changed the rate of Strain adaptation and the disease phenotype upon subsequent serial passaging of PMCA-derived materials in animals. The current studies suggest that replication environment plays an important role in determining the fate of prion Strain adaptation
Giuseppe Tallarida - One of the best experts on this subject based on the ideXlab platform.
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Kinetic changes of ethanolamine base exchange activity and increase of viscosity in sarcolemmal membranes of Hamster heart during development of cardiomyopathy
Molecular and Cellular Biochemistry, 1992Co-Authors: Alba Vecchini, Luciano Binaglia, Paolo Di Nardo, Manuela Bartoli, Marilena Minieri, Giuseppe TallaridaAbstract:The activity of the phospholipid base exchange enzyme specific for ethanolamine has been measured in cardiac sarcolemmal membrane preparations from Syrian golden and UM-X7.1 cardiomyopathic Hamsters. In Syrian golden Hamsters, the Km of the enzyme for ethanolamine does not change with age, whereas it almost doubles in membranes from cardiomyopathic animals, from the 30th to the 150th day of age. During the same period, the membrane cholesterol content increases by 68% in cardiomyopathic Hamsters, whereas it does not change significantly in the Syrian golden Hamster Strain. As a consequence, in the adult animal, the cholesterol to phospholipid ratio and the viscosity of sarcolemmal membranes are higher in UM-X7.1 Strain than in Syrian golden Hamsters. A cause consequence relationship between the enzymatic changes and the compositional modifications in the sarcolemma occurring in UM-X7.1 Hamsters during the development of cardiomyopahhy is proposed. (Mol Cell Biochem 116: 89–93,1992)
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Phospholipid base exchange enzyme activity in sarcolemmal membranes from the heart of cardiomyopathic Hamsters
Molecular and Cellular Biochemistry, 1992Co-Authors: Alba Vecchini, Luciano Binaglia, Paolo Di Nardo, Marilena Minieri, Giuseppe TallaridaAbstract:The activity of phospholipid base exchange enzymes has been evaluated in cardiac sarcolemmal membranes from Syrian Golden Hamsters and from a Hamster Strain (UM-X7.1) characterized by a genetic form of hypertrophic cardiomyopathy. No choline base exchange activity and only a little serine base exchange activity were detected, whereas the ethanolamine base exchange enzyme was found highly active in membranes from both Strains. For this reason, the present study is focussed on the ethanolamine base exchange enzyme. The apparent Km for ethanolamine of ethanolamine base exchange enzyme from Syrian Golden membranes and from UM-X7.1 Strain membranes are 18 and 32 µM, respectively. The specific activity of the sarcolemmal ethanolamine base exchange enzyme is lower in the UM-X7.1 Strain than in Syrian Golden Hamsters. The calcium-dependence of the enzyme appears different when the membranes from the two Strains are compared. Indeed, after removal of the membrane-bound divalent cations, comparable activities are found in both membrane preparations, whereas, upon addition of Ca^2+ to the incubation mixtures, the activity of the enzyme is enhanced in the membranes from Syrian Golden Strain more than in those from UM-X7.1 Strain. The cholesterol content of sarcolemmal membranes is higher in the cardiomyopathic Strain than in the Syrian Golden Hamsters. A possible relation between changes of the membrane lipid composition and of the ethanolamine base exchange activity is discussed.
Kunimi Kikuchi - One of the best experts on this subject based on the ideXlab platform.
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defect of delta sarcoglycan gene is responsible for development of dilated cardiomyopathy of a novel Hamster Strain j2n k calcineurin pp2b activity in the heart of j2n k Hamster
Journal of Biochemistry, 2003Co-Authors: Shinya Mitsuhashi, Naohiro Saito, Keiko Watano, Keiichi Igarashi, Seiichi Tagami, Hiroshi Shima, Kunimi KikuchiAbstract:It has been shown that calcineurin (CN), a serine/threonine protein phosphatase type 2B (PP2B), plays an important role in the development and diseases of cardiac muscles. However, reports on CN activity in dilated cardiomyopathy (DCM) are inconsistent, since there are few good disease models and the measurement of the amount of CN is difficult. Previously, we developed a novel line of DCM Hamster, J2N-k, and its healthy control counterpart, J2N-n, by crossbreeding cardiomyopathy (CM) Hamsters, Bio 14.6, and Golden Hamsters followed by consecutive sib mating. In this study, we identified the DCM-causative gene in J2N-k by analysis of F2 of these two lines, and then we analyzed the change in CN gene expression in the course of the disease, and the change in CN activity using a newly developed method. We show that: (i) the DCM gene of J2N-k Hamster is the delta- sarcoglycan (SG) gene, (ii) CN expression and potential CN activities (CN activity fully activated with Ca(2+) and calmodulin) in the hearts of J2N-k and J2N-n Hamsters are the same levels, (iii) transcription levels of natriuretic peptides, which are augmented by activation of Ca(2+)/calmodulin-dependent enzyme including CN, are significantly increased in the DCM stage in J2N-k Hamster. J2N-k and J2N-n Hamsters will be a useful tool for studying the pathogenesis, therapy, and prevention of human DCM. Although the total amount and potential activity of CN did not change in the cell extracts, targets of CN in vivo were activated in cardiomyocytes of DCM, suggesting that CN activity in the cells is activated by the raising of Ca(2+) concentration in cardiomyocytes of DCM, which is caused by the defect in the delta-SG gene. Our results reveal the complexity of CN regulation in the heart and indicate the need for additional experimentation.
Natallia Makarava - One of the best experts on this subject based on the ideXlab platform.
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Preserving prion Strain identity upon replication of prions in vitro using recombinant prion protein
Acta Neuropathologica Communications, 2018Co-Authors: Natallia Makarava, Regina Savtchenko, Peter Lasch, Michael Beekes, Ilia V. BaskakovAbstract:Last decade witnessed an enormous progress in generating authentic infectious prions or PrP^Sc in vitro using recombinant prion protein (rPrP). Previous work established that rPrP that lacks posttranslational modification is able to support replication of highly infectious PrP^Sc with assistance of cofactors of polyanionic nature and/or lipids. Unexpectedly, previous studies also revealed that seeding of rPrP by brain-derived PrP^Sc gave rise to new prion Strains with new disease phenotypes documenting loss of a Strain identity upon replication in rPrP substrate. Up to now, it remains unclear whether prion Strain identity can be preserved upon replication in rPrP. The current study reports that faithful replication of Hamster Strain SSLOW could be achieved in vitro using rPrP as a substrate. We found that a mixture of phosphatidylethanolamine (PE) and synthetic nucleic acid polyA was sufficient for stable replication of Hamster brain-derived SSLOW PrP^Sc in serial Protein Misfolding Cyclic Amplification (sPMCA) that uses Hamster rPrP as a substrate. The disease phenotype generated in Hamsters upon transmission of recombinant PrP^Sc produced in vitro was strikingly similar to the original SSLOW diseases phenotype with respect to the incubation time to disease, as well as clinical, neuropathological and biochemical features. Infrared microspectroscopy (IR-MSP) indicated that PrP^Sc produced in animals upon transmission of recombinant PrP^Sc is structurally similar if not identical to the original SSLOW PrP^Sc. The current study is the first to demonstrate that rPrP can support replication of brain-derived PrP^Sc while preserving its Strain identity. In addition, the current work is the first to document that successful propagation of a Hamster Strain could be achieved in vitro using Hamster rPrP.
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Prion replication environment defines the fate of prion Strain adaptation.
Public Library of Science (PLoS), 2018Co-Authors: Elizaveta Katorcha, Natallia Makarava, Nuria Gonzalez-montalban, Gabor G Kovacs, Ilia V. BaskakovAbstract:The main risk of emergence of prion diseases in humans is associated with a cross-species transmission of prions of zoonotic origin. Prion transmission between species is regulated by a species barrier. Successful cross-species transmission is often accompanied by Strain adaptation and result in stable changes of Strain-specific disease phenotype. Amino acid sequences of host PrPC and donor PrPSc as well as Strain-specific structure of PrPSc are believed to be the main factors that control species barrier and Strain adaptation. Yet, despite our knowledge of the primary structures of mammalian prions, predicting the fate of prion Strain adaptation is very difficult if possible at all. The current study asked the question whether changes in cofactor environment affect the fate of prions adaptation. To address this question, Hamster Strain 263K was propagated under normal or RNA-depleted conditions using serial Protein Misfolding Cyclic Amplification (PMCA) conducted first in mouse and then Hamster substrates. We found that 263K propagated under normal conditions in mouse and then Hamster substrates induced the disease phenotype similar to the original 263K. Surprisingly, 263K that propagated first in RNA-depleted mouse substrate and then normal Hamster substrate produced a new disease phenotype upon serial transmission. Moreover, 263K that propagated in RNA-depleted mouse and then RNA-depleted Hamster substrates failed to induce clinical diseases for three serial passages despite a gradual increase of PrPSc in animals. To summarize, depletion of RNA in prion replication reactions changed the rate of Strain adaptation and the disease phenotype upon subsequent serial passaging of PMCA-derived materials in animals. The current studies suggest that replication environment plays an important role in determining the fate of prion Strain adaptation
Claude Lutton - One of the best experts on this subject based on the ideXlab platform.
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The Syrian golden Hamster Strain LPN: a useful animal model for human cholelithiasis.
The Journal of nutritional biochemistry, 2002Co-Authors: Murielle M.j Combettes-souverain, Michel Parquet, Maâmar Souidi, Jacqueline Férézou, Michel Riottot, Colette Sérougne, Claude LuttonAbstract:Abstract The purpose of this study was to specify the main mechanisms at the origin of gallstone formation in very young (5-week old) or young adult (9-week old) LPN Hamsters fed a sucrose-rich (normal lipid) lithogenic diet for one and four weeks, respectively. It was also to compare these mechanisms in the two Strains of Hamsters (LPN and Janvier) or when an anti-lithiasic diet was given by substituting 10% of the sucrose by β cyclodextrin. The LPN Strain of Hamsters showed a very high incidence of cholesterol gallstones (73%) after receiving the lithogenic diet. The gallstone formation is very rapid and occurs in less than one week in very young Hamsters which show a high cholesterol synthesis rate in the liver. The cholesterol and phospholipid concentrations in the bile, cholesterol saturation index (CSI) and hydrophobic index (HI) increased significantly, concomitantly with a higher liver cholesterol synthesis in very young Hamsters and with a lower bile acid synthesis (neutral pathway: cholesterol 7α-hydroxylase, CYP7A1 and acidic pathway: sterol 27 hydroxylase, CYP27A1) in young adult Hamsters. No significant changes in the lipoprotein receptor expression (LDLr, SR-BI) were observed after feeding the lithogenic diet. Adding ten per cent β-cyclodextrin, a cyclic oligosaccharide that binds cholesterol and bile acids to the lithogenic diet at the expense of sucrose, induced a decrease in cholesterol bile secretion and in the CSI and HI and prevented cholesterol gallstone formation. Similarly, another Strain of Syrian Golden Hamsters (“ Janvier ”) which originally exhibited a smaller bile cholesterol concentration, lower liver cholesterol synthesis and higher CYP7A1/CYP27A1 activity ratio did not carry cholesterol gallstones when fed the lithogenic diet. The main parameters always found at the origin of cholelithiasis in the Hamster are discussed: a higher hepatic cholesterogenesis (HMGCoAR), a higher HMGCoAR/CYP7A1 activity ratio, a lower cholesterol ester storage capacity, a higher CYP27A1/CYP7A1 activity ratio correlated to a higher cholesterol secretion in the bile and higher CSI and HI. In LPN Hamsters, the incidence of cholesterol gallstones is nil when CSI + HI 0.9. An overall comparison of the data obtained in LPN Hamsters and in Man suggests that this Hamster Strain appears to be an interesting model for human cholelithiasis.
