Evaluation of adenine in anti-inflammation and diabetes

• Main Authors: WU, TZONG-TA, 吳宗達
• Other Authors: CHEN, HAN-MIN
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/2csp5f

博士 === 輔仁大學 === 應用科學與工程研究所博士班 === 107 === Adenine is belong to nucleobases as one of the five members. It can be used as molecular scaffold of may compounds, such as adenosine, nucleotides and cofactors, which participated in an abundance of bio-chemical reactions. The major interest of adenine associated studies are focused on the synthesis of DNA and RNA rather than the regulation of the cell physiology function. In this study, we use two chapters to discuss the evaluation of adenine in anti-inflammation and blood sugar man-agement of diabetes. Pathogenic bacteria induced infection is a risk factor for hospital mortality. Monocyte-derived inflammatory cytokines participate in this progression. The anti-inflammatory effect of adenine has been previously reported by our laboratory and others. However, the mechanism of ac-tion has different opinion and remains unclear in monocyte. Here, ade-nine was found to significantly inhibit the secretion of lipopolysaccharide induced inflammatory cytokines such as TNF-α, IL-1β and IL-6 in THP-1 cells. The bioinformatic analysis results showed that the an-ti-inflammatory function is possibly due to the inhibition of NF-κB sig-naling. And this result is confirmed by immunocytochemistry. Moreover, this effect can be suppressed by the AMP-activated protein kinase (AMPK) inhibitor. Results also showed that adenine can activate AMPK and its multiple downstream targets. Data from mass spectrometry showed that adenine promotes significant elevation of intracellular AMP. Our data in-dicate that the anti-inflammatory mechanism of adenine may involve adenine phosphoribosyltransferase catalyzed intracellular AMP elevation, which stimulates AMPK activation. Diabetes is a group of chronic diseases which classified as losing control of blood sugar level due to the disfunction of insulin regulating system. Type 2 diabetes is commonly present in high income country and region. By using animal model, we found that adenine can improve the ability of blood sugar elevation, and cell model also showed that adenine promote glucose uptake. In sum, it has potential on diabetic medication.