|
KMID : 0613820170270080879
|
|
Journal of Life Science
2017 Volume.27 No. 8 p.879 ~ p.887
|
|
|
Insulin-like Growth Factor-I Modulates BDNF Expression by Inhibition of Histone Deacetylase in C2C12 Skeletal Muscle Cells
|
|
Kim Hye-Jin
Lee Won-Jun
|
|
|
Abstract
|
|
|
|
It is well established that brain-derived neurotrophic factor (BDNF) is expressed not only in the brain but also in skeletal muscle, and is required for normal neuromuscular system function. Histone deacetylases (HDACs) and insulin-like growth factor-I (IGF-I) are potent regulators of skeletal muscle myogenesis and muscle gene expression, but the mechanisms of HDAC and IGF-I in skeletal muscle-derived BDNF expression have not been examined. In this study, we examined the effect of IGF-I and suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor, on BDNF induction. Proliferating or differentiating C2C12 skeletal muscle cells were treated with increasing concentrations (0-50 ng/ml) of IGF-I in the absence or presence of 5 μM SAHA for various time periods (3-24 hr). Treatment of C2C12 cells with IGF-I resulted in a dose- and time-dependent decrease in BDNF mRNA expression. However, inhibition of HDAC led to a significant increase in the expression of BDNF mRNA levels. In addition, immunocytochemistry revealed high BDNF protein levels in undifferentiated C2C12 skeletal muscle cells, whether untreated, IGF-I-treated, or exposed to SAHA. These results represent the first evidence that IGF-I can suppress the mRNA and protein expression of BDNF; conversely, SAHA attenuates the effects of IGF-I. Consequently, SAHA upregulates BDNF expression in C2C12 skeletal muscle cells.
|
|
|
KEYWORD
|
|
|
Brain-derived neurotrophic factor, C2C12 skeletal muscle cell, histone deacetylase inhibitor, insulin-like growth factor-I, suberoylanilide hydroxamic acid
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|