Title
Effects of Astragaloside IV on GSK-3β And S6K1 Phosphorylation via The AKT Pathway in C2C12 Muscle Cells
Presentation Type
Event
Start Date
27-4-2019 8:45 AM
End Date
27-4-2019 9:25 AM
Abstract
Astragaloside IV (AsIV) is the primary active component of the Astragalus membranaceus herb, used in traditional Chinese medicine to treat metabolic disorders. Through in vitro and in vivo experimentation, this saponin phytochemical has been shown to regulate glycogen synthesis through protein kinase B (AKT)-mediated phosphorylation of glycogen synthase kinase 3 beta (GSK-3β). Along with control of glucose homeostasis, AKT activation is an important regulator of protein synthesis via the downstream phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase beta-1 (S6K1). While AsIV has been shown to exhibit metabolic benefits, no study has investigated the possible effect of this compound on protein synthesis. In order to determine the effect of AsIV on protein synthetic pathways, C2C12 murine muscle cells were treated with AsIV and the phosphorylation levels of key enzymes were assessed.
We found that AsIV induced phosphorylation of key protein synthetic targets in a time and dose-dependent manner. By two hours of AsIV treatment, C2C12 cells had the greatest increase in AKT phosphorylation. These cells also had a 1.6-fold increase in GSK-3β phosphorylation and a 4-fold increase in S6K1 activation, compared to controls. However, these effects were not seen when cells were first serum-starved. In addition, AsIV increased phosphorylation levels after cells were initially treated with dexamethasone. These findings help to further understand the molecular changes that occur in muscle cells in response to AsIV and serve as a potential therapeutic mechanism to combat muscle loss.
Effects of Astragaloside IV on GSK-3β And S6K1 Phosphorylation via The AKT Pathway in C2C12 Muscle Cells
Astragaloside IV (AsIV) is the primary active component of the Astragalus membranaceus herb, used in traditional Chinese medicine to treat metabolic disorders. Through in vitro and in vivo experimentation, this saponin phytochemical has been shown to regulate glycogen synthesis through protein kinase B (AKT)-mediated phosphorylation of glycogen synthase kinase 3 beta (GSK-3β). Along with control of glucose homeostasis, AKT activation is an important regulator of protein synthesis via the downstream phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase beta-1 (S6K1). While AsIV has been shown to exhibit metabolic benefits, no study has investigated the possible effect of this compound on protein synthesis. In order to determine the effect of AsIV on protein synthetic pathways, C2C12 murine muscle cells were treated with AsIV and the phosphorylation levels of key enzymes were assessed.
We found that AsIV induced phosphorylation of key protein synthetic targets in a time and dose-dependent manner. By two hours of AsIV treatment, C2C12 cells had the greatest increase in AKT phosphorylation. These cells also had a 1.6-fold increase in GSK-3β phosphorylation and a 4-fold increase in S6K1 activation, compared to controls. However, these effects were not seen when cells were first serum-starved. In addition, AsIV increased phosphorylation levels after cells were initially treated with dexamethasone. These findings help to further understand the molecular changes that occur in muscle cells in response to AsIV and serve as a potential therapeutic mechanism to combat muscle loss.