Agaro-Oligosaccharides Prevent Myostatin Hyperexpression and Myosin Heavy Chain Protein Degradation in C2C12 Myotubes Induced by Tumor Necrosis Factor-α
Myostatin
is a major factor involved in the regulation of skeletal muscle protein mass.
High myostatin levels have been associated with an increase in myotube shrinkage. Enhanced myostatin expression
is caused by pro-catabolic reactions involving compounds such as tumor
necrosis factor (TNF)-α. The present
study investigated the effects of agaro-oligosaccharides (AOSs) on
hypercatabolism of myotubes exposed to TNF-α.
C2C12 myotubes exposed to TNF-α in
the presence or absence of AOSs. Myotube exposure to TNF-α resulted in a reduction in the amount of myosin heavy chain
(MyHC) protein and a decrease in myotube diameter, which was associated with
increased myostatin mRNA expression. AOSs prevented TNF-α-induced MyHC protein loss and restored normal myostatin mRNA
levels, with agarobiose and agarotetraose effectively suppressing the
hyperexpression of the mRNA. In addition, expression levels of the known myostatin
inhibitors, latent transforming growth factor beta binding protein 3 (Ltbp3)
and growth and differentiation factor-associated serum protein 1 (Gasp1) mRNAs,
decreased more in TNF-α-induced
myotubes than in the TNF-α-free
control, possibly resulting in myostatin upregulation. However, AOSs restored
nearly normal expression levels of Ltbp3 and Gasp1 mRNA, potentially
suppressing myostatin expression. These findings suggest that AOSs could
prevent myotube shrinkage induced by TNF-α.
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