The Experts below are selected from a list of 267 Experts worldwide ranked by ideXlab platform
Lorraine Pariset - One of the best experts on this subject based on the ideXlab platform.
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microsatellite genotyping of medieval cattle from central italy suggests an old origin of Chianina and romagnola cattle
Frontiers in Genetics, 2015Co-Authors: Maria Gargani, Lorraine Pariset, Johannes A Lenstra, Elisabetta De Minicis, A ValentiniAbstract:Analysis of DNA from archaeological remains is a valuable tool to interpret the history of ancient animal populations. So far most studies of ancient DNA target mitochondrial DNA (mtDNA), which reveals maternal lineages, but only partially the relationships of current breeds and ancient populations. In this study we explore the feasibility of nuclear DNA analysis. DNA was extracted from 1000-years old cattle bone collected from Ferento, an archaeological site in central Italy. Amplification of 15 microsatellite FAO-recommended markers with PCR products yielded genotypes for four markers. Expected heterozygosity was comparable with values of modern breeds, but observed heterozygosity was underestimated due to allelic loss. Genetic distances suggested a position intermediate between (1) Anatolian, Balkan, Sicilian and South-Italian cattle and (2) the Iberian, North-European and Central-European cattle, but also a clear relationship with two central-Italian breeds, Chianina and Romagnola. This suggests that these breeds are derived from medieval cattle living in the same area. Our results illustrate the potential of ancient DNA for reconstructing the history of local cattle husbandry.
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comparison of milk fat globule membrane mfgm proteins in milk samples of Chianina and holstein cattle breeds across three lactation phases through 2d ief sds page a preliminary study
Food Research International, 2013Co-Authors: Leonardo Murgiano, Angelo Dalessandro, A Valentini, Lello Zolla, Lorraine ParisetAbstract:Abstract Background Characterisation and identification of proteins involved in milk production are important to understand the biology of lactation and to manage dairy cattle selection. Many studies have investigated mammary function, milk secretion and mammary gland involution, but the critical molecular mechanisms implicated are still incomplete. We focused on Milk Fat Globule Membranes (MFGM), a unique subcategory of proteins mainly originating from the Golgi apparatus and endoplasmic reticulum of mammary gland cells. Methods Using a proteomic approach, 2D-IEF SDS PAGE and ESI MS/MS we compared milk MFGM belonging to Chianina and Holstein cattle breeds, representative of selection for meat and milk traits, respectively. Results The two breeds showed different trends in the amount of structural proteins and proteins related to lipid droplet formation, as well as in immunity-related molecules, MFG secretion, mammary gland epithelium apoptosis and mammary gland involution. Conclusions We successfully isolated the major MFGM proteins and monitored their differences between the two breeds, among three different lactation phases and within the same breed across the lactation phases. The detected differences were relative to the amount of proteins involved in lipid deposition into the droplets, immune system and mammary gland cell apoptosis.
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Telomere Length Diversity in Cattle Breeds
Diversity, 2010Co-Authors: Francesca Tilesi, Lorraine Pariset, Alessio Valentini, Enea Gino Di Domenico, Luigi Bosco, Daniela Willems, Fiorentina AscenzioniAbstract:Abstract: Telomeres are specialized nucleoprotein structures that have two important functions: (i) protection of the chromosomal ends from deleterious events such as chromosome fusion and degradation; (ii) counteraction of the “end replication problem” by allowing telomerase-dependent or, more rarely, telomerase-independent telomere elongation. The DNA sequences underlying these activities are short simple tandem repeats, which in vertebrate consist of a variable number of TTAGGG. Telomeres dysfunction may be caused either by the absence of telomerase activity or by mutations in telomeric proteins involved in telomere length and structure regulation. Additionally, increasing experimental evidence suggests that telomeres take part in the complex network regulating cell proliferation. Accordingly, telomeres are involved in biological process such as aging and tumor progression. In this study we determined the telomere length in two bovine Italian cattle breeds, Chianina and Maremmana, which are characterized by high longevity and range breeding. In order to account for possible variation among different tissues, we have determined telomere length in different organs such as spleen, lung and liver. Overall, the median telomere length was significant lower in Chianina (11 ± 0.69 kb) than in Maremmana (12.05 ± 1.57 kb). Moreover, telomere length variation
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comparison of milk fat globule membrane mfgm proteins of Chianina and holstein cattle breed milk samples through proteomics methods
Nutrients, 2009Co-Authors: Leonardo Murgiano, Anna Maria Timperio, A Valentini, Lello Zolla, Silvia Bongiorni, Lorraine ParisetAbstract:Identification of proteins involved in milk production is important to understand the biology of lactation. Many studies have advanced the understanding of mammary function and milk secretion, but the critical molecular mechanisms implicated in milk fat secretion is still incomplete. Milk Fat Globules are secreted from the apical surface of the mammary cells, surrounded by a thin membrane bilayer, the Milk Fat Globule Membrane (MFGM), formed by proteins which have been suggested to be cholesterolemia-lowering factors, inhibitors of cancer cell growth, vitamin binders, bactericidal, suppressors of multiple sclerosis. Using a proteomic approach, we compared MFGM from milk samples of individuals belonging to two different cattle breeds, Chianina and Holstein, representative of selection for milk and meat traits, respectively. We were able to isolate some of the major MFGM proteins in the examined samples and to identify differences between the protein fractions of the two breeds. We detected differences in the amount of proteins linked to mammary gland development and lipid droplets formation, as well as host defence mechanisms. We have shown that proteomics is a suitable, unbiased method for the study of milk fractions proteins and a powerful tool in nutritional genomics.
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comparative proteomics and transcriptomics analyses of livers from two different bos taurus breeds Chianina and holstein friesian
Journal of Proteomics, 2009Co-Authors: Anna Maria Timperio, Angelo Dalessandro, Lorraine Pariset, Gian Maria Damici, A Valentini, Lello ZollaAbstract:The Holstein Friesian and Chianina cattle breeds are representative of extreme selection for milk and meat traits, respectively, with significant changes in metabolism resulting from human selection over the past centuries. In the present study, we wanted to assess whether selection for different purposes has had a measurable effect on liver metabolism through a comparison of the protein and gene expression profiles of the two breeds. We applied 2-DE in order to identify proteins which were differentially expressed in the livers of the two breeds and relate them to different liver functions. We expected to find that only a small number of proteins would be differentially expressed, due to the relatively short phylogenetic distance between these cattle breeds. Nonetheless, thirty nine differentially-expressed proteins were characterized between Chianina and Holstein Friesian, out of a total of 560+/-57 spots that matched. Microarray analyses evidenced the differential expression of 167 genes (148 for the Holstein Friesian and 19 for the Chianina). Despite being closely related at the genetic level, the disparity of the proteomic and transcriptomic profiles of these two breeds allows us to perform pathway analysis thus to pinpoint proteins whose expression might render the latter capable of greater milk production, or proteins involved in altered thermoregulatory ability or hormone production. On the other hand, we found proteins and gene transcripts in Chianina, not expressed in Holstein, which, upon interaction pathway analysis, were mainly involved in anabolic pathways. In brief, our integrated study provides molecular evidences to support the physiological differences between Holstein and Chianina cattle breeds.
A Valentini - One of the best experts on this subject based on the ideXlab platform.
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Skeletal muscle transcriptional profiles in two Italian beef breeds, Chianina and Maremmana, reveal breed specific variation
Molecular Biology Reports, 2016Co-Authors: S. Bongiorni, C. E. M. Gruber, G. Chillemi, S. Bueno, S. Failla, B. Moioli, F. Ferrè, A ValentiniAbstract:Chianina and Maremmana breeds play an important role in the Italian cattle meat market. The Chianina breed is an ancient breed principally raised for draught. Now this breed is the worldwide recognized producer of top quality beef, tasteful and tender, specifically the famous “Florentine steak”. The Maremmana characterized by a massive skeletal structure, is a rustic cattle breed selected for adaptability to the marshy land of the Maremma region. We used a high throughput mRNA sequencing to analyze gene expression in muscle tissues of two Italian cattle breeds, Maremmana (MM) and Chianina (CN) with different selection history. We aim to examine the specific genetic contribution of each breed to meat production and quality, comparing the skeletal muscle tissue from Maremmana and Chianina. Most of the differentially expressed genes were grouped in the Glycolysis/Gluconeogenesis pathways. The rate and the extent of post-mortem energy metabolism have a critical effect on the conversion of muscle to meat. Furthermore, we aim at discovering the differences in nucleotide variation between the two breeds which might be attributable to the different history of selection/divergence. In this work we could emphasize the involvement of pathways of post-mortem energy metabolism. Moreover, we detected a collection of coding SNPs which could offer new genomic resources to improve phenotypic selection in livestock breeding program.
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microsatellite genotyping of medieval cattle from central italy suggests an old origin of Chianina and romagnola cattle
Frontiers in Genetics, 2015Co-Authors: Maria Gargani, Lorraine Pariset, Johannes A Lenstra, Elisabetta De Minicis, A ValentiniAbstract:Analysis of DNA from archaeological remains is a valuable tool to interpret the history of ancient animal populations. So far most studies of ancient DNA target mitochondrial DNA (mtDNA), which reveals maternal lineages, but only partially the relationships of current breeds and ancient populations. In this study we explore the feasibility of nuclear DNA analysis. DNA was extracted from 1000-years old cattle bone collected from Ferento, an archaeological site in central Italy. Amplification of 15 microsatellite FAO-recommended markers with PCR products yielded genotypes for four markers. Expected heterozygosity was comparable with values of modern breeds, but observed heterozygosity was underestimated due to allelic loss. Genetic distances suggested a position intermediate between (1) Anatolian, Balkan, Sicilian and South-Italian cattle and (2) the Iberian, North-European and Central-European cattle, but also a clear relationship with two central-Italian breeds, Chianina and Romagnola. This suggests that these breeds are derived from medieval cattle living in the same area. Our results illustrate the potential of ancient DNA for reconstructing the history of local cattle husbandry.
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comparison of milk fat globule membrane mfgm proteins in milk samples of Chianina and holstein cattle breeds across three lactation phases through 2d ief sds page a preliminary study
Food Research International, 2013Co-Authors: Leonardo Murgiano, Angelo Dalessandro, A Valentini, Lello Zolla, Lorraine ParisetAbstract:Abstract Background Characterisation and identification of proteins involved in milk production are important to understand the biology of lactation and to manage dairy cattle selection. Many studies have investigated mammary function, milk secretion and mammary gland involution, but the critical molecular mechanisms implicated are still incomplete. We focused on Milk Fat Globule Membranes (MFGM), a unique subcategory of proteins mainly originating from the Golgi apparatus and endoplasmic reticulum of mammary gland cells. Methods Using a proteomic approach, 2D-IEF SDS PAGE and ESI MS/MS we compared milk MFGM belonging to Chianina and Holstein cattle breeds, representative of selection for meat and milk traits, respectively. Results The two breeds showed different trends in the amount of structural proteins and proteins related to lipid droplet formation, as well as in immunity-related molecules, MFG secretion, mammary gland epithelium apoptosis and mammary gland involution. Conclusions We successfully isolated the major MFGM proteins and monitored their differences between the two breeds, among three different lactation phases and within the same breed across the lactation phases. The detected differences were relative to the amount of proteins involved in lipid deposition into the droplets, immune system and mammary gland cell apoptosis.
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comparison of milk fat globule membrane mfgm proteins of Chianina and holstein cattle breed milk samples through proteomics methods
Nutrients, 2009Co-Authors: Leonardo Murgiano, Anna Maria Timperio, A Valentini, Lello Zolla, Silvia Bongiorni, Lorraine ParisetAbstract:Identification of proteins involved in milk production is important to understand the biology of lactation. Many studies have advanced the understanding of mammary function and milk secretion, but the critical molecular mechanisms implicated in milk fat secretion is still incomplete. Milk Fat Globules are secreted from the apical surface of the mammary cells, surrounded by a thin membrane bilayer, the Milk Fat Globule Membrane (MFGM), formed by proteins which have been suggested to be cholesterolemia-lowering factors, inhibitors of cancer cell growth, vitamin binders, bactericidal, suppressors of multiple sclerosis. Using a proteomic approach, we compared MFGM from milk samples of individuals belonging to two different cattle breeds, Chianina and Holstein, representative of selection for milk and meat traits, respectively. We were able to isolate some of the major MFGM proteins in the examined samples and to identify differences between the protein fractions of the two breeds. We detected differences in the amount of proteins linked to mammary gland development and lipid droplets formation, as well as host defence mechanisms. We have shown that proteomics is a suitable, unbiased method for the study of milk fractions proteins and a powerful tool in nutritional genomics.
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comparative proteomics and transcriptomics analyses of livers from two different bos taurus breeds Chianina and holstein friesian
Journal of Proteomics, 2009Co-Authors: Anna Maria Timperio, Angelo Dalessandro, Lorraine Pariset, Gian Maria Damici, A Valentini, Lello ZollaAbstract:The Holstein Friesian and Chianina cattle breeds are representative of extreme selection for milk and meat traits, respectively, with significant changes in metabolism resulting from human selection over the past centuries. In the present study, we wanted to assess whether selection for different purposes has had a measurable effect on liver metabolism through a comparison of the protein and gene expression profiles of the two breeds. We applied 2-DE in order to identify proteins which were differentially expressed in the livers of the two breeds and relate them to different liver functions. We expected to find that only a small number of proteins would be differentially expressed, due to the relatively short phylogenetic distance between these cattle breeds. Nonetheless, thirty nine differentially-expressed proteins were characterized between Chianina and Holstein Friesian, out of a total of 560+/-57 spots that matched. Microarray analyses evidenced the differential expression of 167 genes (148 for the Holstein Friesian and 19 for the Chianina). Despite being closely related at the genetic level, the disparity of the proteomic and transcriptomic profiles of these two breeds allows us to perform pathway analysis thus to pinpoint proteins whose expression might render the latter capable of greater milk production, or proteins involved in altered thermoregulatory ability or hormone production. On the other hand, we found proteins and gene transcripts in Chianina, not expressed in Holstein, which, upon interaction pathway analysis, were mainly involved in anabolic pathways. In brief, our integrated study provides molecular evidences to support the physiological differences between Holstein and Chianina cattle breeds.
Lello Zolla - One of the best experts on this subject based on the ideXlab platform.
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comparison of milk fat globule membrane mfgm proteins in milk samples of Chianina and holstein cattle breeds across three lactation phases through 2d ief sds page a preliminary study
Food Research International, 2013Co-Authors: Leonardo Murgiano, Angelo Dalessandro, A Valentini, Lello Zolla, Lorraine ParisetAbstract:Abstract Background Characterisation and identification of proteins involved in milk production are important to understand the biology of lactation and to manage dairy cattle selection. Many studies have investigated mammary function, milk secretion and mammary gland involution, but the critical molecular mechanisms implicated are still incomplete. We focused on Milk Fat Globule Membranes (MFGM), a unique subcategory of proteins mainly originating from the Golgi apparatus and endoplasmic reticulum of mammary gland cells. Methods Using a proteomic approach, 2D-IEF SDS PAGE and ESI MS/MS we compared milk MFGM belonging to Chianina and Holstein cattle breeds, representative of selection for meat and milk traits, respectively. Results The two breeds showed different trends in the amount of structural proteins and proteins related to lipid droplet formation, as well as in immunity-related molecules, MFG secretion, mammary gland epithelium apoptosis and mammary gland involution. Conclusions We successfully isolated the major MFGM proteins and monitored their differences between the two breeds, among three different lactation phases and within the same breed across the lactation phases. The detected differences were relative to the amount of proteins involved in lipid deposition into the droplets, immune system and mammary gland cell apoptosis.
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Chianina beef tenderness investigated through integrated omics
Journal of Proteomics, 2012Co-Authors: Angelo Dalessandro, Cristina Marrocco, Sara Rinalducci, Cristiana Mirasole, Sebastiana Failla, Lello ZollaAbstract:In the present study we performed an integrated proteomics, interactomics and metabolomics analysis of Longissimus dorsi tender and tough meat samples from Chianina beef cattle. Results were statistically handled as to obtain Pearson's correlation coefficients of the results from Omics investigation in relation to canonical tenderness-related parameters, including Warner Bratzler shear force, myofibrillar degradation (at 48 h and 10 days after slaughter), sarcomere length and total collagen content. As a result, we could observe that the tender meat group was characterized by higher levels of glycolytic enzymes, which were over-phosphorylated and produced accumulation of glycolytic intermediates. Oxidative stress promoted meat tenderness and elicited heat shock protein responses, which in turn triggered apoptosis-like cascades along with PARP fragmentation. Phosphorylation was found to be a key process in post mortem muscle conversion to meat, as it was shown not only to modulate glycolytic enzyme activities, but also mediate the stability of structural proteins at the Z-disk. On the other hand, phosphorylation of HSPs has been supposed to alter their functions through changing their affinity for target interactors. Analogies and breed-specific differences are highlighted throughout the text via a direct comparison of the present results against the ones obtained in a parallel study on Maremmana Longissimus dorsi. It emerges that, while the main cornerstones and the final outcome are maintained, post mortem metabolism in tender and tough meat yielding individuals is subtly modulated via specific higher levels of enzymes and amino acidic residue phosphorylation in a breed-specific fashion, and whether calcium homeostasis dysregulation was a key factor in Maremmana, higher early post mortem phosphocreatine levels in the Chianina tender group could favor a slower and prolonged glycolytic rate, prolonging the extent of the minimum hanging period necessary to obtain tender meat from this breed by a few days. This article is part of a Special Issue entitled: Farm animal proteomics.
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Analysis of the cattle liver proteome by high-sensitive liquid chromatography coupled with mass spectrometry method.
Methods of Molecular Biology, 2012Co-Authors: Anna Maria Timperio, Gian Maria D’amici, Lello ZollaAbstract:The present chapter describes methods for the separation and identification of proteins in liver metabolism through a comparison of the protein expression profiles of the two breeds taken into account as a model: Holstein Friesian and Chianina cattle. The liver has received special attention, containing as it does, enzymes involved in energy generation, carbohydrate, lipid, amino acid, and xenobiotic metabolism, as well as proteins involved in polypeptide synthesis, folding, and cell structure. The first step in the procedure is the preparation of purified protein fractions from liver tissues, followed by sample preparation for 2-DE analysis in order to identify proteins which could be differentially expressed in the livers of the two breeds and relate them to different liver functions. Data can be then statistically elaborated with cluster analysis, which stressed the up-/on-regulation trend of these proteins. Quantitative data can be used to perform a two-way hierarchical cluster analysis of the 39 differentially expressed protein spots, either up- or on-regulated in Chianina versus Holstein Friesian liver samples. Thus, spots from 2-DE maps can be carefully excised from the gel and subjected to in-gel trypsin digestion and analyzed by tandem mass spectrometry in their contents.
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comparison of milk fat globule membrane mfgm proteins of Chianina and holstein cattle breed milk samples through proteomics methods
Nutrients, 2009Co-Authors: Leonardo Murgiano, Anna Maria Timperio, A Valentini, Lello Zolla, Silvia Bongiorni, Lorraine ParisetAbstract:Identification of proteins involved in milk production is important to understand the biology of lactation. Many studies have advanced the understanding of mammary function and milk secretion, but the critical molecular mechanisms implicated in milk fat secretion is still incomplete. Milk Fat Globules are secreted from the apical surface of the mammary cells, surrounded by a thin membrane bilayer, the Milk Fat Globule Membrane (MFGM), formed by proteins which have been suggested to be cholesterolemia-lowering factors, inhibitors of cancer cell growth, vitamin binders, bactericidal, suppressors of multiple sclerosis. Using a proteomic approach, we compared MFGM from milk samples of individuals belonging to two different cattle breeds, Chianina and Holstein, representative of selection for milk and meat traits, respectively. We were able to isolate some of the major MFGM proteins in the examined samples and to identify differences between the protein fractions of the two breeds. We detected differences in the amount of proteins linked to mammary gland development and lipid droplets formation, as well as host defence mechanisms. We have shown that proteomics is a suitable, unbiased method for the study of milk fractions proteins and a powerful tool in nutritional genomics.
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comparative proteomics and transcriptomics analyses of livers from two different bos taurus breeds Chianina and holstein friesian
Journal of Proteomics, 2009Co-Authors: Anna Maria Timperio, Angelo Dalessandro, Lorraine Pariset, Gian Maria Damici, A Valentini, Lello ZollaAbstract:The Holstein Friesian and Chianina cattle breeds are representative of extreme selection for milk and meat traits, respectively, with significant changes in metabolism resulting from human selection over the past centuries. In the present study, we wanted to assess whether selection for different purposes has had a measurable effect on liver metabolism through a comparison of the protein and gene expression profiles of the two breeds. We applied 2-DE in order to identify proteins which were differentially expressed in the livers of the two breeds and relate them to different liver functions. We expected to find that only a small number of proteins would be differentially expressed, due to the relatively short phylogenetic distance between these cattle breeds. Nonetheless, thirty nine differentially-expressed proteins were characterized between Chianina and Holstein Friesian, out of a total of 560+/-57 spots that matched. Microarray analyses evidenced the differential expression of 167 genes (148 for the Holstein Friesian and 19 for the Chianina). Despite being closely related at the genetic level, the disparity of the proteomic and transcriptomic profiles of these two breeds allows us to perform pathway analysis thus to pinpoint proteins whose expression might render the latter capable of greater milk production, or proteins involved in altered thermoregulatory ability or hormone production. On the other hand, we found proteins and gene transcripts in Chianina, not expressed in Holstein, which, upon interaction pathway analysis, were mainly involved in anabolic pathways. In brief, our integrated study provides molecular evidences to support the physiological differences between Holstein and Chianina cattle breeds.
Francesco Mascarello - One of the best experts on this subject based on the ideXlab platform.
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Structural study of skeletal muscle fibres in healthy and pseudomyotonia affected cattle.
Annals of Anatomy-anatomischer Anzeiger, 2016Co-Authors: Francesco Mascarello, Roberta SacchettoAbstract:Summary Cattle congenital pseudomyotonia (PMT), recognized as naturally occurring animal model of human Brody disease, is an inherited recessive autosomal muscular disorder due to missense mutations in ATP2A1 gene, encoding sarco(endo)plasmic reticulum Ca 2+ -ATPase protein, isoform 1 (SERCA1). PMT has been described in the Chianina and Romagnola italian cattle breeds and as a single case in Dutch improved Red and White cross-breed. The genetic defect turned out to be heterogeneous in different cattle breeds, even though clinical symptoms were homogeneous. Skeletal muscles of affected animals are characterized by a selective deficiency of SERCA1 in sarcoplasmic reticulum (SR) membranes. Recently, we provided evidence that in Chianina breed, the ubiquitin proteasome system is responsible for SERCA1 mutant premature disposal, even when the mutation does not affect the catalytic properties of the pump. Results presented here show that all SERCA1 mutants described until now, although expressed at low level, are correctly targeted to SR membranes. Ultrastructural studies confirm that in pathological muscle fibres, structure, as well as triads, is well preserved. All together these results suggest that a possible therapeutical approach based on the rescue of the defective protein at SR membranes could be hypothesized. Only fully functionally active missense mutants, whem located at the SR membrane could restore the efficient control of Ca 2+ homeostasis and prevent the appearance of the pathological signs. Moreover, these data demonstrate the increasing importance of domestic animals as genetic models of human pathologies.
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inhibition of ubiquitin proteasome system rescues the defective sarco endo plasmic reticulum ca2 atpase serca1 protein causing Chianina cattle pseudomyotonia
Journal of Biological Chemistry, 2014Co-Authors: Elisa Bianchini, Stefania Testoni, A Gentile, Francesco Mascarello, Tito Cali, Denis Ottolini, Antonello Villa, Marisa Brini, R Betto, Poul NissenAbstract:A missense mutation in ATP2A1 gene, encoding sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) protein, causes Chianina cattle congenital pseudomyotonia, an exercise-induced impairment of muscle relaxation. Skeletal muscles of affected cattle are characterized by a selective reduction of SERCA1 in sarcoplasmic reticulum membranes. In this study, we provide evidence that the ubiquitin proteasome system is involved in the reduced density of mutated SERCA1. The treatment with MG132, an inhibitor of ubiquitin proteasome system, rescues the expression level and membrane localization of the SERCA1 mutant in a heterologous cellular model. Cells co-transfected with the Ca(2+)-sensitive probe aequorin show that the rescued SERCA1 mutant exhibits the same ability of wild type to maintain Ca(2+) homeostasis within cells. These data have been confirmed by those obtained ex vivo on adult skeletal muscle fibers from a biopsy from a pseudomyotonia-affected subject. Our data show that the mutation generates a protein most likely corrupted in proper folding but not in catalytic activity. Rescue of mutated SERCA1 to sarcoplasmic reticulum membrane can re-establish resting cytosolic Ca(2+) concentration and prevent the appearance of pathological signs of cattle pseudomyotonia.
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a defective serca1 protein is responsible for congenital pseudomyotonia in Chianina cattle
American Journal of Pathology, 2009Co-Authors: Roberta Sacchetto, Stefania Testoni, Cord Drogemuller, A Gentile, M Rossi, Ernesto Damiani, Rocco Liguori, Francesco MascarelloAbstract:Recently, a muscular disorder defined as "congenital pseudomyotonia" was described in Chianina cattle, one of the most important Italian cattle breeds for quality meat and leather. The clinical phenotype of this disease is characterized by an exercise-induced muscle contracture that prevents animals from performing muscular activities. On the basis of clinical symptoms, Chianina pseudomyotonia appeared related to human Brody's disease, a rare inherited disorder of skeletal muscle function that results from a sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1) deficiency caused by a defect in the ATP2A1 gene that encodes SERCA1. SERCA1 is involved in transporting calcium from the cytosol to the lumen of the sarcoplasmic reticulum. Recently, we identified the genetic defect underlying Chianina cattle pseudomyotonia. A missense mutation in exon 6 of the ATP2A1 gene, leading to an R164H substitution in the SERCA1 protein, was found. In this study, we provide biochemical evidence for a selective deficiency in SERCA1 protein levels in sarcoplasmic reticulum membranes from affected muscles, although mRNA levels are unaffected. The reduction of SERCA1 levels accounts for the reduced Ca(2+)-ATPase activity without any significant change in Ca(2+)-dependency. The loss of SERCA1 is not compensated for by the expression of the SERCA2 isoform. We believe that Chianina cattle pseudomyotonia might, therefore, be the true counterpart of human Brody's disease, and that bovine species might be used as a suitable animal model.
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identification of a missense mutation in the bovine atp2a1 gene in congenital pseudomyotonia of Chianina cattle an animal model of human brody disease
Genomics, 2008Co-Authors: Cord Drogemuller, Stefania Testoni, Michaela Drogemuller, Tosso Leeb, Francesco Mascarello, M Rossi, Arcangelo Gentile, Ernesto Damiani, Roberta SacchettoAbstract:Congenital pseudomyotonia in Chianina cattle is a muscle function disorder very similar to that of Brody disease in humans. Mutations in the human ATP2A1 gene, encoding SERCA1, cause Brody myopathy. The analysis of the collected Chianina pedigree data suggested monogenic autosomal recessive inheritance and revealed that all 17 affected individuals traced back to a single founder. A deficiency of SERCA1 function in skeletal muscle of pseudomyotonia affected Chianina cattle was observed as SERCA1 activity in affected animals was decreased by about 70%. Linkage analysis showed that the mutation was located in the ATP2A1 gene region on BTA25 and subsequent mutation analysis of the ATP2A1 exons revealed a perfectly associated missense mutation in exon 6 (c.491G>A) leading to a p.Arg164His substitution. Arg164 represents a functionally important and strongly conserved residue of SERCA1. This study provides a suitable large animal model for human Brody disease.
Roberta Sacchetto - One of the best experts on this subject based on the ideXlab platform.
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Structural study of skeletal muscle fibres in healthy and pseudomyotonia affected cattle.
Annals of Anatomy-anatomischer Anzeiger, 2016Co-Authors: Francesco Mascarello, Roberta SacchettoAbstract:Summary Cattle congenital pseudomyotonia (PMT), recognized as naturally occurring animal model of human Brody disease, is an inherited recessive autosomal muscular disorder due to missense mutations in ATP2A1 gene, encoding sarco(endo)plasmic reticulum Ca 2+ -ATPase protein, isoform 1 (SERCA1). PMT has been described in the Chianina and Romagnola italian cattle breeds and as a single case in Dutch improved Red and White cross-breed. The genetic defect turned out to be heterogeneous in different cattle breeds, even though clinical symptoms were homogeneous. Skeletal muscles of affected animals are characterized by a selective deficiency of SERCA1 in sarcoplasmic reticulum (SR) membranes. Recently, we provided evidence that in Chianina breed, the ubiquitin proteasome system is responsible for SERCA1 mutant premature disposal, even when the mutation does not affect the catalytic properties of the pump. Results presented here show that all SERCA1 mutants described until now, although expressed at low level, are correctly targeted to SR membranes. Ultrastructural studies confirm that in pathological muscle fibres, structure, as well as triads, is well preserved. All together these results suggest that a possible therapeutical approach based on the rescue of the defective protein at SR membranes could be hypothesized. Only fully functionally active missense mutants, whem located at the SR membrane could restore the efficient control of Ca 2+ homeostasis and prevent the appearance of the pathological signs. Moreover, these data demonstrate the increasing importance of domestic animals as genetic models of human pathologies.
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a defective serca1 protein is responsible for congenital pseudomyotonia in Chianina cattle
American Journal of Pathology, 2009Co-Authors: Roberta Sacchetto, Stefania Testoni, Cord Drogemuller, A Gentile, M Rossi, Ernesto Damiani, Rocco Liguori, Francesco MascarelloAbstract:Recently, a muscular disorder defined as "congenital pseudomyotonia" was described in Chianina cattle, one of the most important Italian cattle breeds for quality meat and leather. The clinical phenotype of this disease is characterized by an exercise-induced muscle contracture that prevents animals from performing muscular activities. On the basis of clinical symptoms, Chianina pseudomyotonia appeared related to human Brody's disease, a rare inherited disorder of skeletal muscle function that results from a sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1) deficiency caused by a defect in the ATP2A1 gene that encodes SERCA1. SERCA1 is involved in transporting calcium from the cytosol to the lumen of the sarcoplasmic reticulum. Recently, we identified the genetic defect underlying Chianina cattle pseudomyotonia. A missense mutation in exon 6 of the ATP2A1 gene, leading to an R164H substitution in the SERCA1 protein, was found. In this study, we provide biochemical evidence for a selective deficiency in SERCA1 protein levels in sarcoplasmic reticulum membranes from affected muscles, although mRNA levels are unaffected. The reduction of SERCA1 levels accounts for the reduced Ca(2+)-ATPase activity without any significant change in Ca(2+)-dependency. The loss of SERCA1 is not compensated for by the expression of the SERCA2 isoform. We believe that Chianina cattle pseudomyotonia might, therefore, be the true counterpart of human Brody's disease, and that bovine species might be used as a suitable animal model.
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identification of a missense mutation in the bovine atp2a1 gene in congenital pseudomyotonia of Chianina cattle an animal model of human brody disease
Genomics, 2008Co-Authors: Cord Drogemuller, Stefania Testoni, Michaela Drogemuller, Tosso Leeb, Francesco Mascarello, M Rossi, Arcangelo Gentile, Ernesto Damiani, Roberta SacchettoAbstract:Congenital pseudomyotonia in Chianina cattle is a muscle function disorder very similar to that of Brody disease in humans. Mutations in the human ATP2A1 gene, encoding SERCA1, cause Brody myopathy. The analysis of the collected Chianina pedigree data suggested monogenic autosomal recessive inheritance and revealed that all 17 affected individuals traced back to a single founder. A deficiency of SERCA1 function in skeletal muscle of pseudomyotonia affected Chianina cattle was observed as SERCA1 activity in affected animals was decreased by about 70%. Linkage analysis showed that the mutation was located in the ATP2A1 gene region on BTA25 and subsequent mutation analysis of the ATP2A1 exons revealed a perfectly associated missense mutation in exon 6 (c.491G>A) leading to a p.Arg164His substitution. Arg164 represents a functionally important and strongly conserved residue of SERCA1. This study provides a suitable large animal model for human Brody disease.