The Experts below are selected from a list of 108 Experts worldwide ranked by ideXlab platform
Juan Maria Torres - One of the best experts on this subject based on the ideXlab platform.
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Molecular Alterations in the Cerebellum of Sporadic Creutzfeldt–Jakob Disease Subtypes with DJ-1 as a Key Regulator of Oxidative Stress
Molecular Neurobiology, 2018Co-Authors: Waqas Tahir, Saima Zafar, Franc Llorens, Amandeep Singh Arora, Katrin Thüne, Matthias Schmitz, Nadine Gotzmann, Niels Kruse, Brit Mollenhauer, Juan Maria TorresAbstract:Cerebellar damage and granular and Purkinje cell loss in sporadic Creutzfeldt–Jakob disease (sCJD) highlight a critical involvement of the cerebellum during symptomatic progression of the disease. In this project, global proteomic alterations in the cerebellum of brain from the two most prevalent subtypes (MM1 and VV2) of sCJD were studied. Two-dimensional gel electrophoresis (2DE) coupled mass spectrometric identification revealed 40 Proteins in MM1 and 43 Proteins in VV2 subtype to be differentially expressed. Of those, 12 Proteins showed common differential expression in their expression between two subtypes. Differentially expressed Proteins mainly belonged to (i) cell cycle, gene expression and cell death; (ii) cellular stress response/oxidative stress (OS) and (iii) signal transduction and synaptic functions, related molecular functions. We verified 10 differentially expressed Proteins at transcriptional and translational level as well. Interestingly, Protein Deglycase DJ-1 (an antioxidative Protein) showed an increase in its messenger RNA (mRNA) expression in both MM1 and VV2 subtypes but Protein expression only in VV2 subtype in cerebellum of sCJD patients. Nuclear translocalization of DJ-1 confirmed its expressional alteration due to OS in sCJD. Downstream experiments showed the activation of nuclear factor erythroid-2 related factor 2 (Nrf2)/antioxidative response element (ARE) pathway. DJ-1 Protein concentration was significantly increased during the clinical phase in cerebrospinal fluid of sCJD patients and also at presymptomatic and symptomatic stages in cerebellum of humanized PrP transgenic mice inoculated with sCJD (MM1 and VV2) brain. These results suggest the implication of oxidative stress during the pathophysiology of sCJD.
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Molecular Alterations in the Cerebellum of Sporadic Creutzfeldt-Jakob Disease Subtypes with DJ-1 as a Key Regulator of Oxidative Stress.
Molecular Neurobiology, 2018Co-Authors: Waqas Tahir, Saima Zafar, Franc Llorens, Amandeep Singh Arora, Katrin Thüne, Matthias Schmitz, Nadine Gotzmann, Niels Kruse, Brit Mollenhauer, Juan Maria TorresAbstract:Cerebellar damage and granular and Purkinje cell loss in sporadic Creutzfeldt-Jakob disease (sCJD) highlight a critical involvement of the cerebellum during symptomatic progression of the disease. In this project, global proteomic alterations in the cerebellum of brain from the two most prevalent subtypes (MM1 and VV2) of sCJD were studied. Two-dimensional gel electrophoresis (2DE) coupled mass spectrometric identification revealed 40 Proteins in MM1 and 43 Proteins in VV2 subtype to be differentially expressed. Of those, 12 Proteins showed common differential expression in their expression between two subtypes. Differentially expressed Proteins mainly belonged to (i) cell cycle, gene expression and cell death; (ii) cellular stress response/oxidative stress (OS) and (iii) signal transduction and synaptic functions, related molecular functions. We verified 10 differentially expressed Proteins at transcriptional and translational level as well. Interestingly, Protein Deglycase DJ-1 (an antioxidative Protein) showed an increase in its messenger RNA (mRNA) expression in both MM1 and VV2 subtypes but Protein expression only in VV2 subtype in cerebellum of sCJD patients. Nuclear translocalization of DJ-1 confirmed its expressional alteration due to OS in sCJD. Downstream experiments showed the activation of nuclear factor erythroid-2 related factor 2 (Nrf2)/antioxidative response element (ARE) pathway. DJ-1 Protein concentration was significantly increased during the clinical phase in cerebrospinal fluid of sCJD patients and also at presymptomatic and symptomatic stages in cerebellum of humanized PrP transgenic mice inoculated with sCJD (MM1 and VV2) brain. These results suggest the implication of oxidative stress during the pathophysiology of sCJD.
Oliver Schilling - One of the best experts on this subject based on the ideXlab platform.
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Proteomic Profiling of Cardiomyocyte-Specific Cathepsin A Overexpression Links Cathepsin A to the Oxidative Stress Response.
Journal of proteome research, 2016Co-Authors: Agnese Petrera, Dominik Linz, Mathias Hohl, Ursula Kern, Alejandro Gomez-auli, Johann Gassenhuber, Thorsten Sadowski, Oliver SchillingAbstract:Cathepsin A (CTSA) is a lysosomal carboxypeptidase present at the cell surface and secreted outside the cell. Additionally, CTSA binds to β-galactosidase and neuraminidase 1 to protect them from degradation. CTSA has gained attention as a drug target for the treatment of cardiac hypertrophy and heart failure. Here, we investigated the impact of CTSA on the murine cardiac proteome in a mouse model of cardiomyocyte-specific human CTSA overexpression using liquid chromatography-tandem mass spectrometry in conjunction with an isotopic dimethyl labeling strategy. We identified up to 2000 Proteins in each of three biological replicates. Statistical analysis by linear models for microarray data (limma) found >300 significantly affected Proteins (moderated p-value ≤0.01), thus establishing CTSA as a key modulator of the cardiac proteome. CTSA strongly impaired the balance of the proteolytic system by upregulating several proteases such as cathepsin B, cathepsin D, and cathepsin Z while down-regulating numerous protease inhibitors. Moreover, cardiomyocyte-specific human CTSA overexpression strongly reduced the levels of numerous antioxidative stress Proteins, i.e., peroxiredoxins and Protein Deglycase DJ-1. In vitro, using cultured rat cardiomyocytes, ectopic overexpression of CTSA resulted in accumulation of reactive oxygen species. Collectively, our proteomic and functional data strengthen an association of CTSA with the cellular oxidative stress response.
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Proteomic Profiling of Cardiomyocyte-Specific Cathepsin A Overexpression Links Cathepsin A to the Oxidative Stress Response
2016Co-Authors: Agnese Petrera, Dominik Linz, Mathias Hohl, Ursula Kern, Alejandro Gomez-auli, Johann Gassenhuber, Thorsten Sadowski, Oliver SchillingAbstract:Cathepsin A (CTSA) is a lysosomal carboxypeptidase present at the cell surface and secreted outside the cell. Additionally, CTSA binds to β-galactosidase and neuraminidase 1 to protect them from degradation. CTSA has gained attention as a drug target for the treatment of cardiac hypertrophy and heart failure. Here, we investigated the impact of CTSA on the murine cardiac proteome in a mouse model of cardiomyocyte-specific human CTSA overexpression using liquid chromatography–tandem mass spectrometry in conjunction with an isotopic dimethyl labeling strategy. We identified up to 2000 Proteins in each of three biological replicates. Statistical analysis by linear models for microarray data (limma) found >300 significantly affected Proteins (moderated p-value ≤0.01), thus establishing CTSA as a key modulator of the cardiac proteome. CTSA strongly impaired the balance of the proteolytic system by upregulating several proteases such as cathepsin B, cathepsin D, and cathepsin Z while down-regulating numerous protease inhibitors. Moreover, cardiomyocyte-specific human CTSA overexpression strongly reduced the levels of numerous antioxidative stress Proteins, i.e., peroxiredoxins and Protein Deglycase DJ-1. In vitro, using cultured rat cardiomyocytes, ectopic overexpression of CTSA resulted in accumulation of reactive oxygen species. Collectively, our proteomic and functional data strengthen an association of CTSA with the cellular oxidative stress response
Waqas Tahir - One of the best experts on this subject based on the ideXlab platform.
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Molecular Alterations in the Cerebellum of Sporadic Creutzfeldt–Jakob Disease Subtypes with DJ-1 as a Key Regulator of Oxidative Stress
Molecular Neurobiology, 2018Co-Authors: Waqas Tahir, Saima Zafar, Franc Llorens, Amandeep Singh Arora, Katrin Thüne, Matthias Schmitz, Nadine Gotzmann, Niels Kruse, Brit Mollenhauer, Juan Maria TorresAbstract:Cerebellar damage and granular and Purkinje cell loss in sporadic Creutzfeldt–Jakob disease (sCJD) highlight a critical involvement of the cerebellum during symptomatic progression of the disease. In this project, global proteomic alterations in the cerebellum of brain from the two most prevalent subtypes (MM1 and VV2) of sCJD were studied. Two-dimensional gel electrophoresis (2DE) coupled mass spectrometric identification revealed 40 Proteins in MM1 and 43 Proteins in VV2 subtype to be differentially expressed. Of those, 12 Proteins showed common differential expression in their expression between two subtypes. Differentially expressed Proteins mainly belonged to (i) cell cycle, gene expression and cell death; (ii) cellular stress response/oxidative stress (OS) and (iii) signal transduction and synaptic functions, related molecular functions. We verified 10 differentially expressed Proteins at transcriptional and translational level as well. Interestingly, Protein Deglycase DJ-1 (an antioxidative Protein) showed an increase in its messenger RNA (mRNA) expression in both MM1 and VV2 subtypes but Protein expression only in VV2 subtype in cerebellum of sCJD patients. Nuclear translocalization of DJ-1 confirmed its expressional alteration due to OS in sCJD. Downstream experiments showed the activation of nuclear factor erythroid-2 related factor 2 (Nrf2)/antioxidative response element (ARE) pathway. DJ-1 Protein concentration was significantly increased during the clinical phase in cerebrospinal fluid of sCJD patients and also at presymptomatic and symptomatic stages in cerebellum of humanized PrP transgenic mice inoculated with sCJD (MM1 and VV2) brain. These results suggest the implication of oxidative stress during the pathophysiology of sCJD.
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Molecular Alterations in the Cerebellum of Sporadic Creutzfeldt-Jakob Disease Subtypes with DJ-1 as a Key Regulator of Oxidative Stress.
Molecular Neurobiology, 2018Co-Authors: Waqas Tahir, Saima Zafar, Franc Llorens, Amandeep Singh Arora, Katrin Thüne, Matthias Schmitz, Nadine Gotzmann, Niels Kruse, Brit Mollenhauer, Juan Maria TorresAbstract:Cerebellar damage and granular and Purkinje cell loss in sporadic Creutzfeldt-Jakob disease (sCJD) highlight a critical involvement of the cerebellum during symptomatic progression of the disease. In this project, global proteomic alterations in the cerebellum of brain from the two most prevalent subtypes (MM1 and VV2) of sCJD were studied. Two-dimensional gel electrophoresis (2DE) coupled mass spectrometric identification revealed 40 Proteins in MM1 and 43 Proteins in VV2 subtype to be differentially expressed. Of those, 12 Proteins showed common differential expression in their expression between two subtypes. Differentially expressed Proteins mainly belonged to (i) cell cycle, gene expression and cell death; (ii) cellular stress response/oxidative stress (OS) and (iii) signal transduction and synaptic functions, related molecular functions. We verified 10 differentially expressed Proteins at transcriptional and translational level as well. Interestingly, Protein Deglycase DJ-1 (an antioxidative Protein) showed an increase in its messenger RNA (mRNA) expression in both MM1 and VV2 subtypes but Protein expression only in VV2 subtype in cerebellum of sCJD patients. Nuclear translocalization of DJ-1 confirmed its expressional alteration due to OS in sCJD. Downstream experiments showed the activation of nuclear factor erythroid-2 related factor 2 (Nrf2)/antioxidative response element (ARE) pathway. DJ-1 Protein concentration was significantly increased during the clinical phase in cerebrospinal fluid of sCJD patients and also at presymptomatic and symptomatic stages in cerebellum of humanized PrP transgenic mice inoculated with sCJD (MM1 and VV2) brain. These results suggest the implication of oxidative stress during the pathophysiology of sCJD.
Agnese Petrera - One of the best experts on this subject based on the ideXlab platform.
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Proteomic Profiling of Cardiomyocyte-Specific Cathepsin A Overexpression Links Cathepsin A to the Oxidative Stress Response.
Journal of proteome research, 2016Co-Authors: Agnese Petrera, Dominik Linz, Mathias Hohl, Ursula Kern, Alejandro Gomez-auli, Johann Gassenhuber, Thorsten Sadowski, Oliver SchillingAbstract:Cathepsin A (CTSA) is a lysosomal carboxypeptidase present at the cell surface and secreted outside the cell. Additionally, CTSA binds to β-galactosidase and neuraminidase 1 to protect them from degradation. CTSA has gained attention as a drug target for the treatment of cardiac hypertrophy and heart failure. Here, we investigated the impact of CTSA on the murine cardiac proteome in a mouse model of cardiomyocyte-specific human CTSA overexpression using liquid chromatography-tandem mass spectrometry in conjunction with an isotopic dimethyl labeling strategy. We identified up to 2000 Proteins in each of three biological replicates. Statistical analysis by linear models for microarray data (limma) found >300 significantly affected Proteins (moderated p-value ≤0.01), thus establishing CTSA as a key modulator of the cardiac proteome. CTSA strongly impaired the balance of the proteolytic system by upregulating several proteases such as cathepsin B, cathepsin D, and cathepsin Z while down-regulating numerous protease inhibitors. Moreover, cardiomyocyte-specific human CTSA overexpression strongly reduced the levels of numerous antioxidative stress Proteins, i.e., peroxiredoxins and Protein Deglycase DJ-1. In vitro, using cultured rat cardiomyocytes, ectopic overexpression of CTSA resulted in accumulation of reactive oxygen species. Collectively, our proteomic and functional data strengthen an association of CTSA with the cellular oxidative stress response.
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Proteomic Profiling of Cardiomyocyte-Specific Cathepsin A Overexpression Links Cathepsin A to the Oxidative Stress Response
2016Co-Authors: Agnese Petrera, Dominik Linz, Mathias Hohl, Ursula Kern, Alejandro Gomez-auli, Johann Gassenhuber, Thorsten Sadowski, Oliver SchillingAbstract:Cathepsin A (CTSA) is a lysosomal carboxypeptidase present at the cell surface and secreted outside the cell. Additionally, CTSA binds to β-galactosidase and neuraminidase 1 to protect them from degradation. CTSA has gained attention as a drug target for the treatment of cardiac hypertrophy and heart failure. Here, we investigated the impact of CTSA on the murine cardiac proteome in a mouse model of cardiomyocyte-specific human CTSA overexpression using liquid chromatography–tandem mass spectrometry in conjunction with an isotopic dimethyl labeling strategy. We identified up to 2000 Proteins in each of three biological replicates. Statistical analysis by linear models for microarray data (limma) found >300 significantly affected Proteins (moderated p-value ≤0.01), thus establishing CTSA as a key modulator of the cardiac proteome. CTSA strongly impaired the balance of the proteolytic system by upregulating several proteases such as cathepsin B, cathepsin D, and cathepsin Z while down-regulating numerous protease inhibitors. Moreover, cardiomyocyte-specific human CTSA overexpression strongly reduced the levels of numerous antioxidative stress Proteins, i.e., peroxiredoxins and Protein Deglycase DJ-1. In vitro, using cultured rat cardiomyocytes, ectopic overexpression of CTSA resulted in accumulation of reactive oxygen species. Collectively, our proteomic and functional data strengthen an association of CTSA with the cellular oxidative stress response
Franc Llorens - One of the best experts on this subject based on the ideXlab platform.
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Molecular Alterations in the Cerebellum of Sporadic Creutzfeldt–Jakob Disease Subtypes with DJ-1 as a Key Regulator of Oxidative Stress
Molecular Neurobiology, 2018Co-Authors: Waqas Tahir, Saima Zafar, Franc Llorens, Amandeep Singh Arora, Katrin Thüne, Matthias Schmitz, Nadine Gotzmann, Niels Kruse, Brit Mollenhauer, Juan Maria TorresAbstract:Cerebellar damage and granular and Purkinje cell loss in sporadic Creutzfeldt–Jakob disease (sCJD) highlight a critical involvement of the cerebellum during symptomatic progression of the disease. In this project, global proteomic alterations in the cerebellum of brain from the two most prevalent subtypes (MM1 and VV2) of sCJD were studied. Two-dimensional gel electrophoresis (2DE) coupled mass spectrometric identification revealed 40 Proteins in MM1 and 43 Proteins in VV2 subtype to be differentially expressed. Of those, 12 Proteins showed common differential expression in their expression between two subtypes. Differentially expressed Proteins mainly belonged to (i) cell cycle, gene expression and cell death; (ii) cellular stress response/oxidative stress (OS) and (iii) signal transduction and synaptic functions, related molecular functions. We verified 10 differentially expressed Proteins at transcriptional and translational level as well. Interestingly, Protein Deglycase DJ-1 (an antioxidative Protein) showed an increase in its messenger RNA (mRNA) expression in both MM1 and VV2 subtypes but Protein expression only in VV2 subtype in cerebellum of sCJD patients. Nuclear translocalization of DJ-1 confirmed its expressional alteration due to OS in sCJD. Downstream experiments showed the activation of nuclear factor erythroid-2 related factor 2 (Nrf2)/antioxidative response element (ARE) pathway. DJ-1 Protein concentration was significantly increased during the clinical phase in cerebrospinal fluid of sCJD patients and also at presymptomatic and symptomatic stages in cerebellum of humanized PrP transgenic mice inoculated with sCJD (MM1 and VV2) brain. These results suggest the implication of oxidative stress during the pathophysiology of sCJD.
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Molecular Alterations in the Cerebellum of Sporadic Creutzfeldt-Jakob Disease Subtypes with DJ-1 as a Key Regulator of Oxidative Stress.
Molecular Neurobiology, 2018Co-Authors: Waqas Tahir, Saima Zafar, Franc Llorens, Amandeep Singh Arora, Katrin Thüne, Matthias Schmitz, Nadine Gotzmann, Niels Kruse, Brit Mollenhauer, Juan Maria TorresAbstract:Cerebellar damage and granular and Purkinje cell loss in sporadic Creutzfeldt-Jakob disease (sCJD) highlight a critical involvement of the cerebellum during symptomatic progression of the disease. In this project, global proteomic alterations in the cerebellum of brain from the two most prevalent subtypes (MM1 and VV2) of sCJD were studied. Two-dimensional gel electrophoresis (2DE) coupled mass spectrometric identification revealed 40 Proteins in MM1 and 43 Proteins in VV2 subtype to be differentially expressed. Of those, 12 Proteins showed common differential expression in their expression between two subtypes. Differentially expressed Proteins mainly belonged to (i) cell cycle, gene expression and cell death; (ii) cellular stress response/oxidative stress (OS) and (iii) signal transduction and synaptic functions, related molecular functions. We verified 10 differentially expressed Proteins at transcriptional and translational level as well. Interestingly, Protein Deglycase DJ-1 (an antioxidative Protein) showed an increase in its messenger RNA (mRNA) expression in both MM1 and VV2 subtypes but Protein expression only in VV2 subtype in cerebellum of sCJD patients. Nuclear translocalization of DJ-1 confirmed its expressional alteration due to OS in sCJD. Downstream experiments showed the activation of nuclear factor erythroid-2 related factor 2 (Nrf2)/antioxidative response element (ARE) pathway. DJ-1 Protein concentration was significantly increased during the clinical phase in cerebrospinal fluid of sCJD patients and also at presymptomatic and symptomatic stages in cerebellum of humanized PrP transgenic mice inoculated with sCJD (MM1 and VV2) brain. These results suggest the implication of oxidative stress during the pathophysiology of sCJD.