| Autor: |
Cheng-Hui Fang, Bingguo Li, James, J. Howard, Yahya, Ayesha, Kadeer, Nijiati, Xialing Guo, Chun Xiao, Supp, Dorothy M., Kagan, Richard J., Hasselgren, Per-Olof, Sheriff, Sulaiman |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Regulatory, Integrative & Comparative Physiology; Oct2007, Vol. 293, pR1545-R1551, 7p |
| Abstrakt: |
Previous reports suggest that burn-induced muscle proteolysis can be inhibited by treatment with GSK-3β inhibitors, suggesting that burn injury may be associated with increased GSK-3β activity. The influence of burn injury on muscle GSK-3β activity, however, is not known. We determined the effect of a 30% total body surface full-thickness burn injury in rats on muscle GSK-3β activity by measuring GSK-3β activity and tissue levels of serine 9 phosphorylated GSK-3β, p(Ser9)-GSK-3β, by Western blot analysis and immunohistochemistry. Because burn-induced muscle wasting is, at least in part, mediated by glucocorticoids, we used dexamethasone-treated cultured muscle cells in which GSK-3β expression was reduced with small interfering RNA (siRNA) to further assess the role of GSK-3β in muscle atrophy. Burn injury resulted in a seven-fold increase in GSK-3β activity in skeletal muscle. This effect of burn was accompanied by reduced tissue levels of p(Ser9)-GSK-3β, suggesting that burn injury stimulates GSK-3β in skeletal muscle secondary to inhibited phosphorylation of the enzyme. In addition, burn injury resulted in inhibited phosphorylation and activation of Akt, an upstream regulatory mechanism of GSK-3β activity. Reducing the expression of GSK-3β in cultured muscle cells with siRNA inhibited dexamethasone-induced protein degradation by -50%. The results suggest that burn injury stimulates GSK-3β activity in skeletal muscle and that GSK-3β may, at least in part, regulate glucocorticoidmediated muscle wasting. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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