Date of Award

5-2019

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Biology

Thesis Sponsor/Dissertation Chair/Project Chair

Mitchell Sitnick

Committee Member

Quinn Vega

Committee Member

John Gaynor

Abstract

Saponins are a broad class of functionally diverse phytochemicals that have been shown to exhibit antihyperglycemic, antihyperlipidemic, anti-inflammatory, and anticancer effects. Through in vitro and in vivo experimentation, Astragaloside IV (AsIV) 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 also an important regulator of protein synthesis via the downstream phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase beta-1 (S6K1). Because AsIV can activate this pathway to stimulate glucose metabolism, it is possible that it can also promote protein synthesis as well since these two regulatory processes utilize the same pathway. 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-dependent manner, with the greatest increases in phosphorylation after two hours of AsIV treatment. However, this effect was not seen when cells were serum-starved prior to AsIV treatment. Lastly, AsIV was able to increase GSK-3β phosphorylation in cells treated with dexamethasone first. These findings help to further understand the molecular changes that occur in muscle cells treated with AsIV.

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