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Dexamethasone-induced skeletal muscle atrophy was associated with upregulation of myostatin promoter activity

Author:
Qin, Jian, Du, Rong, Yang, Ya-Qun, Zhang, Hong-Qiang, Li, Qing, Liu, Lin, Guan, Hong, Hou, Jian, An, Xiao-Rong
Source:
Research in veterinary science 2013 v.94 no.1 pp. 84-89
ISSN:
0034-5288
Subject:
body weight, dexamethasone, gene expression, glucocorticoid receptors, mice, muscular atrophy, mutation, myostatin, response elements, skeletal muscle, ultrastructure
Abstract:
Some recent studies showed that the glucocorticoid-induced muscle atrophy was associated with myostatin, a negative regulator of skeletal muscle. In this study, two experiments were performed to investigate the relationship between the glucocorticoid-induced ultrastructural changes in skeletal muscle and the myostatin gene expression, and to examine in vivo whether the glucocorticoid-induced upregulation of myostatin gene expression is associated with the myostatin promoter activity. In the first experiment, the Kun-Ming mice with similar body weights were treated with high-dose dexamethasone. The results showed that high-dose dexamethasone caused myofibrillar disorganization or degradation and mitochondrial swelling or vacuolization, which were accompanied with the upregulation of myostatin expression. In the second experiment, the mice were treated with the wild-type or GRE (glucocorticoid response elements)-mutant myostatin promoter vector and high-dose dexamethasone alone or together with RU486. The results showed that the mutation of GRE motif resulted in the obvious decrease of the myostatin promoter activity, the high-dose dexamethasone promoted significantly the activity of the wild-type myostatin promoter but did not affect the activity of the GRE-mutant myostatin promoter, and RU486 inhibited the effect of dexamethasone on the wild-type myostatin promoter activity. Taken together, these results suggested that the dexamethasone-induced changes in ultrastructure of skeletal muscle were associated with the upregulation of myostatin gene expression and the upregulation was partly attributed to the binding of glucocorticoid receptor to GRE motifs along myostatin promoter.
Agid:
1140779