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Myostatin (MSTN) and transforming growth factor-ß1 (TGF-ß1) belong to the same TGF-ß superfamily of proteins. They are involved in regulation of skeletal muscle growth and development as well as muscle catabolism. The aim of the present study was to investigate the relationship between mstn and TGF-ß1 expression in proliferating and differentiating mouse C2C12 myoblasts cultured in normal and catabolic conditions and to evaluate the effect of exogenous TGF-ß1 as well as "knock down" of TGF-ß1 receptor type II on mstn expression in proliferating and differentiating myogenic cells. The direct effect of TGF-ß1 on myostatin was also examined. Myostatin expression increased gradually with cell confluency in proliferating cultures, while the level of TGF-ß1, detected in the form of a 100 kDa small latent complex diminished. Myostatin expression was accompanied by a partial cell cycle arrest. Three forms of myostatin were found: a 52 kDa precursor, a 40 kDa latency associated propeptide, and a 26 kDa active peptide. A decrease in myostatin and TGF-ß1 levels was observed during the first three days of differentiation, which was subsequently followed by significant increase of their expression during next three to four days of differentiation. Catabolic state induced by dexamethasone significantly increased the level of all forms of myostatin as well as latent (100 kDa) and active (25 kDa) forms of TGF-ß1 in differentiating myoblasts in a dose dependent manner. Exogenous TGF-ß1 (2 ng/ml) significantly increased myostatin levels both in proliferating and differentiating C2C12 myoblasts, whereas silencing of the TGF-ß1 receptor II gene significantly lowered myostatin level in examined cells. The presented results indicate that TGF-ß1 may control myostatin-related regulation of myogenesis through up-regulation of myostatin, predominantly in the course of terminal differentiation and glucocorticoid-dependent catabolic stimulation.
Microsatellites within genes have become important because of their association with genetic diseases in humans. A novel microsatellite was identified in the first intron of the bovine myostatin gene. It is characterized by a mononucleotide core motif that exhibits polymorphic sequence variants (from 12 to 21 repeats) within and between some bovine breeds. Structural analysis of the microsatellite region in bovines as well as in closely related species permitted to trace the possible mechanisms for its structural evolution across the order Artiodactyla.
The progress in molecular genetics in animal breeding is moderately effective as compared to traditional animal breeding using quantitative genetic approaches. There is an extensive disparity between the number of reported quantitative trait loci (QTLs) and their linked genetic variations in cattle, pig, and chicken. The identification of causative mutations affecting quantitative traits is still very challenging and hampered by the cloudy relationship between genotype and phenotype. There are relatively few reports in which a successful identification of a causative mutation for an animal production trait was demonstrated. The examples that have attracted considerable attention from the animal breeding community are briefly summarized and presented in a table. In this mini-review, the recent progress in mapping quantitative trait nucleotides (QTNs) are reviewed, including the ABCG2 gene mutation that underlies a QTL for fat and protein content and the ovine MSTN gene mutation that causes muscular hypertrophy in Texel sheep. It is concluded that the pi ogress in molecular genetics might facilitate the elucidation of the genetic architecture of QTLs, so that also the high-hanging fruits can be harvested in order to contribute to efficient and sustainable animal production.
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