17 research outputs found

    Differential expression of the RTP/Drg1/Ndr1 gene product in proliferating and growth arrested cells

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    AbstractUsing a differential display method to identify differentiation-related genes in human myelomonocytic U937 cells, we cloned the cDNA of a gene identical to Drg1 and homologous to other recently discovered genes, respectively human RTP and Cap43 and mouse Ndr1 and TDD5 genes. Their open reading frames encode proteins highly conserved between mouse and man but which do not share homology with other know proteins. Conditions in which mRNAs are up-regulated suggest a role for the protein in cell growth arrest and terminal differentiation. We raised antibodies against a synthetic peptide reproducing a characteristic sequence of the putative polypeptide chain. These antibodies revealed a protein with the expected 43 kDa molecular mass, up-regulated by phorbol ester, retinoids and 1,25-(OH)2 vitamin D3 in U937 cells. It was increased in mammary carcinoma MCF-7 cells treated by retinoids and by the anti-estrogen ICI 182,780 but not by 4-hydroxytamoxifen. The mouse Drg1 homologous protein was up-regulated by retinoic acid in C2 myogenic cells. The diversity of situations in which expression of RTP/Drg1/Ndr1 has now been observed shows that it is widely distributed and up-regulated by various agents. Here we show that ligands of nuclear transcription factors involved in cell differentiation are among the inducers of this novel protein

    Magneto-Luminescence Correlation in the Textbook Dysprosium(III) Nitrate Single-Ion Magnet

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    Multifunctional Single-Molecule Magnets (SMMs) or Single-Ion Magnets (SIMs) are intriguing molecule-based materials presenting an association of the slow magnetic relaxation with other physical properties. In this article, we present an example of a very simple molecule based on Dy3+ ion exhibiting a field induced SIM property and a characteristic Dy3+ based emission. The [Dy(NO3)(3)(H2O)(4)]center dot 2H(2)O (1) complex is characterized by the means of single crystal X-Ray diffraction and their magnetic and photo-luminescent properties are investigated. We demonstrate here that it is possible to correlate the magnetic and luminescent properties and to obtain the Orbach barrier from the low temperature emission spectra, which is often difficult to properly extract from the magnetic measurements, especially in the case of field induced SIMs

    Myostatin: a negative regulator of muscle development and maintenance

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    International audienceMyostatin is a member of the TGF beta family which plays a major role in negative regulation of muscle development. Not only do mstn-/-mice display a dramatic increase in skeletal muscle mass, cattle harboring loss of function mutations in the myostatin gene also exhibit muscle overdevelopment associated to a shift in the contractile and metabolic features of muscles fibers. The occurrence of such mutations associated to increased muscle mass in humans has also been reported. Recent data clearly suggest that myostatin is also involved in muscle tissue maintenance in adults, in particular by activating pathways leading to proteolysis and satellite cell activity. As myostatin expression generally increases during muscle atrophy, some promising attempts have been made to improve the behavior of some muscle pathologies, such as myopathies, by targeting myostatin activity. These attempts have opened the way for novel pharmacological strategies focused on skeletal muscle diseases. Here we review the physiopathological consequences of changes in myostatin expression and their clinical interest. We also briefly address the myostatin molecular pathway by describing the knowledge which makes it possible to test the efficiency of pharmacological inhibition of this growth factor activity in muscle pathologies

    The myostatin gene: physiology and pharmacological relevance

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    International audienceMyostatin, which was cloned in 1997, is a potent inhibitor of skeletal muscle growth and member of the tumour growth factor-beta family. Disruption of the myostatin gene in mice induces a dramatic increase in muscle mass, caused by a combination of hypertrophy and hyperplasia. Natural mutations occurring in cattle were also associated with a significant increase in muscle mass and, recently, an inactivating myostatin mutation associated with the same phenotype was identified in humans. Studies into the molecular basis of this antimyogenic influence led to the conclusion that myostatin inhibits myoblast proliferation and differentiation through a classical tumour growth factor-beta pathway involving the activin receptor ActRIIB and Smads 2 and 3. Approaches that induce myostatin depletion or inactivation have led to a significant improvement in muscle regeneration processes, especially in degenerative diseases, through stimulation of satellite cell proliferation and differentiation. These promising data open the way to new therapeutic approaches in muscle diseases through targeting of the myostatin pathway

    Myostatin regulation of muscle development: Molecular basis, natural mutations, physiopathological aspects

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    International audienceSince its identification in 1997, myostatin has been considered as a novel and unique negative regulator of muscle growth, as mstn-/- mice display a dramatic and widespread increase in skeletal muscle mass. Myostatin also appears to be involved in muscle homeostasis in adults as its expression is regulated during muscle atrophy. Moreover, deletion of the myostatin gene seems to affect adipose tissue mass in addition to skeletal muscle mass. Natural myostatin gene mutations occur in cattle breeds such as Belgian Blue, exhibiting an obviously increased muscle mass, but also in humans, as has recently been demonstrated. Here we review these natural mutations and their associated phenotypes as well as the physiological influence of the alterations in myostatin expression and the physiopathological consequences of changes in myostatin expression, especially with regard to satellite cells. Interestingly, studies have demonstrated some rescue effects of myostatin in muscular pathologies such as myopathies, providing a novel pharmacological strategy for treatment. Furthermore, the myostatin pathway is now better understood thanks to in vitro studies and it consists of inhibition of myoblast progression in the cell cycle, inhibition of myoblast terminal differentiation, in both cases associated to protection from apoptosis. The molecular pathway driving the myogenic myostatin influence is currently under extensive study and many molecular partners of myostatin have been identified, suggesting novel potent muscle growth enhancers for both human and agricultural applications

    Phosphinic acids as inorganic bridging ligands for the 1D self-assembly of Mn(II) complexes

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    International audienceThe construction of supramolecular structures by self-assembly of metal complexes and linkers has attracted a broad interest during the last decade. Tetradendate ligands like salen derivatives, phthlocyanines or porphyrins, which are able to block the equatorial positions of octahedral metals, have been used for the preparation of 1D structures. In this communication, we will report the use of phosphinic acids as linkers for the construction of 1D polymeric chains by self-assembling manganese (III) complexes of salen ligands. Depending on the nature of the salen ligand and the phosphinate derivatives, monomeric, dimeric or polymeric structures have been obtained. The magnetic properties of these compounds will be reported

    PRIMER NOTE Characterization of polymorphic microsatellite loci within a young Boophilus microplus metapopulation

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    Nine microsatellite loci from the cattle tick Boophilus microplus were isolated and characterized within New Caledonia. This Pacific island was invaded by the cattle tick from a few immigration events dating from mid-20th century. A population survey involving 94 adult ticks indicated monomorphism at one locus, presence of null alleles at another, and high genetic diversity (0.61–0.72) at seven loci apparently suitable for population genetics studies. This opens the opportunity to dissect the populational mechanisms involved in the spectacular capacity of B. microplus to cope with local environmental heterogeneity during its recurrent invasions of tropical areas
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