Differential expression of O-linked-N-acetylglucosamine modified proteins and their interaction with epigenome in 3T3-L1 preadipocytes and adipocytes

• Main Authors: Jui-Ming Su, 蘇芮敏
• Other Authors: Tusty-Jiuan Hsieh
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/08087353072513281230

碩士 === 高雄醫學大學 === 醫學遺傳學研究所 === 100 === According to the report from WTO, obesity has been one of the most popular chronic diseases in the world, and leads to hypertension, cardiovascular disease, diabetes and hyperlipidemia. In 2011, six out of Taiwan top 10 causes of death are associated with obesity. Obesity is formed by adipocyte proliferation and hypertrophy. When preadipocyte differentiates to adipocyte, lipid is accumulated in 3T3-L1 cells of mouse. Research indicates that the Hexosamine Biosynthesis Pathway (HBP) downstream, which produces O-GlcNAc protein modification, has been proven to take part in the regulation of PPARγ and C / EBP-β during adipocyte differentiation. Recent report of epigenomic researches have shown that histone 3 K4, K27, and K9 modifications regulate adipocyte differentiation, and DNA CpG island methylation has been described to regulate cell differentiation. Our study aimed to investigate the interation between O-GlcNAc protein modification and epigenomic regulation during adipocyte differentiation. We also use proteomic analysis to discover O-GlcNAc modification protein. We want to identify the physiological and pathological role of O-GlcNAc modified proteins during preadipocyte differentiate to adipocyte. Our experiments showed that H3K4 methylation and H3K27 acetylation were increased during adipogenesis and inhibition of HBP activity prevented these two Histone 3 modifications. We also found that DNMT1 expression was increased when HBP was inhibited. Using proteomic analysis, we found the protein compositions were different during preadipocyte differentiate to adipocyte. We identified some O-GlcNAc modified proteins in preadipocytes and adipocytes, by camparing with dbOGAP database. Howerer, the function of these O-GlcNAc modified proteins in adipogenesis still needs further investigation.