Increased Muscle Stress-Sensitivity Induced by Selenoprotein N Inactivation in Mouse: A Mammalian Model for SEPN1-Related Myopathy

Rederstorff, Mathieu; Castets, Perrine; Arbogast, Sandrine; Lainé, Jeanne; Vassilopoulos, Stéphane; Beuvin, Maud; Dubourg, Odile; Vignaud, Alban; Ferry, Arnaud; Krol, Alain; Allamand, Valérie; Guicheney, Pascale; Ferreiro, Ana; Lescure, Alain

doi:10.1371/journal.pone.0023094

Cited by 64 publications

(65 citation statements)

References 46 publications

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“…Recent studies using a zebrafish animal model revealed that SelN is required for early muscle development and differentiation in this organism (77,165). More recently, SelN Ϫ/Ϫ mice were developed (50,293). However, in contrast to what was observed in zebrafish, no abnormalities were found in the structure and the size of muscle fibers in SelN knockout mice.…”

Section: K Selenoprotein Nmentioning

confidence: 98%

Selenoproteins: Molecular Pathways and Physiological Roles

Labunskyy

Hatfield

Gladyshev³

2014

Physiological Reviews

1,028

835

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Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by selenium-containing proteins (selenoproteins) that are present in all three domains of life. Although selenoproteins represent diverse molecular pathways and biological functions, all these proteins contain at least one selenocysteine (Sec), a seleniumcontaining amino acid, and most serve oxidoreductase functions. Sec is cotranslationally inserted into nascent polypeptide chains in response to the UGA codon, whose normal function is to terminate translation. To decode UGA as Sec, organisms evolved the Sec insertion machinery that allows incorporation of this amino acid at specific UGA codons in a process requiring a cis-acting Sec insertion sequence (SECIS) element. Although the basic mechanisms of Sec synthesis and insertion into proteins in both prokaryotes and eukaryotes have been studied in great detail, the identity and functions of many selenoproteins remain largely unknown. In the last decade, there has been significant progress in characterizing selenoproteins and selenoproteomes and understanding their physiological functions. We discuss current knowledge about how these unique proteins perform their functions at the molecular level and highlight new insights into the roles that selenoproteins play in human health.

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Section: K Selenoprotein Nmentioning

confidence: 98%

Selenoproteins: Molecular Pathways and Physiological Roles

Labunskyy

Hatfield

Gladyshev³

2014

Physiological Reviews

1,028

835

View full text Add to dashboard Cite

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“…Loss of SEPN1 function is associated with increased oxidative stress in muscle [103], accelerated muscle pathology in the setting of physiologic stressors [104], and with abnormalities in muscle stem cells [105].…”

Section: Sepn1-related Myopathiesmentioning

confidence: 99%

Triadopathies: An Emerging Class of Skeletal Muscle Diseases

2014

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The triad is a skeletal muscle substructure responsible for the regulation of excitation-contraction coupling. It is formed by the close apposition of the T-tubule and the terminal sarcoplasmic reticulum. A rapidly growing list of skeletal myopathies, here referred to as triadopathies, are caused by gene mutations in components of the triad. These disorders, at their root, are caused by defects in excitation contraction coupling and intracellular calcium homeostasis. Secondary abnormalities in triad structure and/or function are also reported in several muscle diseases, most notably certain muscular dystrophies. This review highlights the current understanding of both primary and secondary triadopathies, and identifies important concepts yet to be fully addressed in the field. The emphasis of the review is both on the pathogenesis of triadopathies and their potential treatment.

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“…These include reports on mice lacking functional genes for SelK [26], GPx2 [102], GPx3 [103], SelN [104], and SelR [105]. We are currently not aware of any publications on constitutive knockout mice for genes encoding Txnrd3, SelH, SelI, SelO, SelS, SelT, SelV, SelW, or SPS2.…”

Section: Constitutive Knockout Mice Studiesmentioning

confidence: 99%

Selenoproteins in Nervous System Development and Function

Pitts

Byrns

Ogawa-Wong

et al. 2014

Biol Trace Elem Res

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Selenoproteins are a distinct class of proteins that are characterized by the co-translational incorporation of selenium (Se) in the form of the 21st amino acid selenocysteine. Selenoproteins provide a key defense against oxidative stress, as many of these proteins participate in oxidation-reduction reactions neutralizing reactive oxygen species, where selenocysteine residues act as catalytic sites. Many selenoproteins are highly expressed in the brain and mouse knockout studies have determined that several are required for normal brain development. In parallel with these laboratory studies, recent reports of rare human cases with mutations in genes involved in selenoprotein biosynthesis have described individuals with an assortment of neurological problems that mirror those detailed in knockout mice. These deficits include impairments in cognition and motor function, seizures, hearing loss, and altered thyroid metabolism. Additionally, due to the fact that oxidative stress is a key feature of neurodegenerative disease, there is considerable interest in the therapeutic potential of selenium supplementation for human neurological disorders. Studies performed in cell culture and rodent models have demonstrated that selenium administration attenuates oxidative stress, prevents neurodegeneration, and counters cell signaling mechanisms known to be dysregulated in certain disease states. However, there is currently no definitive evidence in support of selenium supplementation to prevent and/or treat common neurological conditions in the general population. It appears likely, that in humans, supplementation with selenium may only benefit certain subpopulations, such as those that are either selenium-deficient or possess genetic variants that affect selenium metabolism.

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Increased Muscle Stress-Sensitivity Induced by Selenoprotein N Inactivation in Mouse: A Mammalian Model for SEPN1-Related Myopathy

Cited by 64 publications

References 46 publications

Selenoproteins: Molecular Pathways and Physiological Roles

Selenoproteins: Molecular Pathways and Physiological Roles

Triadopathies: An Emerging Class of Skeletal Muscle Diseases

Selenoproteins in Nervous System Development and Function

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