Page 8 - ebook

[A. Biochemistry/Molecular Biology] A-4

Proteomic approach reveals inhibition of glycolysis and

mevalonate pathway by oxysterol treatment in liver

Wan-Seog Shim¹, Chanhee Lee¹, Jong Hyuk Yoon², Parkyong Song¹*

¹Department of Convergence Medical Sciences, Pusan National University School of Medicine, Yangsan 50612,

Korea, ²Neurodegenerative Disease Research Group, Korea Brain Research Insititute, Daegu 41068, Korea

Oxysterols are oxygenated derivatives of cholesterol that are intermediates or even end products in cholesterol

excretion pathways. As an oxysterol, compound A is known to regulate endothelial inflammation and cancer
progression. However, few studies are available how compound A affects cellular proteomic profiles and metabolic

pathway in liver. To analyze systemic effects of compound A in liver, we performed liquid chromatography-tandem
mass spectrometry (LC-MS/MS) using normal liver cell line. KEGG pathway analysis proved that some metabolic

pathways such as cholesterol biosynthesis and glycolysis were significantly reduced by compound A treatment.
Additionally, transcripts analysis further supported that the compound A inhibited gene expression, which related

to mevalonate, lipogenesis, and glycolysis pathway in mouse hepatic cell line. Because accumulation of cholesterol
and lipid promotes hepatic fatty liver disease, and increased glycolysis contributes to triacylglycerol maturation, the

suppressive effects of compound a in hepatic lipid synthetic pathway may provide protective effects against fatty
liver development.