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      Implications for the mammalian sialidases in the physiopathology of skeletal muscle

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          Abstract

          The family of mammalian sialidases is composed of four distinct versatile enzymes that remove negatively charged terminal sialic acid residues from gangliosides and glycoproteins in different subcellular areas and organelles, including lysosomes, cytosol, plasma membrane and mitochondria. In this review we summarize the growing body of data describing the important role of sialidases in skeletal muscle, a complex apparatus involved in numerous key functions and whose functional integrity can be affected by various conditions, such as aging, chronic diseases, cancer and neuromuscular disorders. In addition to supporting the proper catabolism of glycoconjugates, sialidases can affect different signaling pathways by desialylation of many receptors and modulation of ganglioside content in cell membranes, thus actively participating in myoblast proliferation, differentiation and hypertrophy, insulin responsiveness and skeletal muscle architecture.

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          Most cited references119

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          Signaling in muscle atrophy and hypertrophy.

          Muscle performance is influenced by turnover of contractile proteins. Production of new myofibrils and degradation of existing proteins is a delicate balance, which, depending on the condition, can promote muscle growth or loss. Protein synthesis and protein degradation are coordinately regulated by pathways that are influenced by mechanical stress, physical activity, availability of nutrients, and growth factors. Understanding the signaling that regulates muscle mass may provide potential therapeutic targets for the prevention and treatment of muscle wasting in metabolic and neuromuscular diseases.
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            Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle.

            Aging skeletal muscles suffer a steady decline in mass and functional performance, and compromised muscle integrity as fibrotic invasions replace contractile tissue, accompanied by a characteristic loss in the fastest, most powerful muscle fibers. The same programmed deficits in muscle structure and function are found in numerous neurodegenerative syndromes and disease-related cachexia. We have generated a model of persistent, functional myocyte hypertrophy using a tissue-restricted transgene encoding a locally acting isoform of insulin-like growth factor-1 that is expressed in skeletal muscle (mIgf-1). Transgenic embryos developed normally, and postnatal increases in muscle mass and strength were not accompanied by the additional pathological changes seen in other Igf-1 transgenic models. Expression of GATA-2, a transcription factor normally undetected in skeletal muscle, marked hypertrophic myocytes that escaped age-related muscle atrophy and retained the proliferative response to muscle injury characteristic of younger animals. The preservation of muscle architecture and age-independent regenerative capacity through localized mIgf-1 transgene expression suggests clinical strategies for the treatment of age or disease-related muscle frailty.
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              Bioactive sphingolipids: metabolism and function.

              Sphingolipids (SLs) are essential constituents of eukaryotic cells. Besides playing structural roles in cellular membranes, some metabolites, including ceramide, sphingosine, and sphingosine-1-phosphate, have drawn attention as bioactive signaling molecules involved in the regulation of cell growth, differentiation, senescence, and apoptosis. Understanding the many cell regulatory functions of SL metabolites requires an advanced knowledge of how and where in the cell they are generated, converted, or degraded. This review will provide a short overview of the metabolism, localization, and compartmentalization of SLs. Also, a discussion on bioactive members of the SL family and inducers of SL enzymes that lead to ceramide generation will be presented.
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                Author and article information

                Journal
                Skelet Muscle
                Skelet Muscle
                Skeletal Muscle
                BioMed Central
                2044-5040
                2012
                1 November 2012
                : 2
                : 23
                Affiliations
                [1 ]Department of Biomedical Sciences and Biotechnologies and Interuniversitary Institute of Myology (IIM), University of Brescia, Viale Europa 11, 25123, Brescia, Italy
                [2 ]Department of Medical Biotechnology and Translational Medicine, University of Milan, Segrate, Milan, Italy
                [3 ]Laboratory of Stem Cell for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy
                [4 ]Stem Cell Research Institute, University Hospital Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium
                [5 ]Human Anatomy Section, University of Pavia, Via Forlanini 8, 27100, Pavia, Italy
                Article
                2044-5040-2-23
                10.1186/2044-5040-2-23
                3534598
                23114189
                1b0deac0-3f82-4566-bebf-b7585395f420
                Copyright ©2012 Fanzani et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 July 2012
                : 2 October 2012
                Categories
                Review

                Rheumatology
                glycoproteins,gangliosides,myogenesis,skeletal muscle,sialidases
                Rheumatology
                glycoproteins, gangliosides, myogenesis, skeletal muscle, sialidases

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