Mechanism Involved in Inhibition of High Concentration of Glucose on The Proliferation of Chinese Hamster Ovary Cells

• Main Authors: Ming-Chen Yu, 俞銘誠
• Other Authors: Ching-Ping Tseng
• Format: Others
• Language: en_US
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/18925491733638045489

碩士 === 國立交通大學 === 生物科技研究所 === 89 === The high glucose concentration inhibits Chinese Hamster Ovary (CHO) cell growth but the mechanism is still unclear. In previous studies, we found that the cell growth rate decreased from 1.3/day to 0.9/day when cells were grew in 10 g/L glucose concentration. In addition, the glucose consumption rate, lactate production rate, and the intracellular cAMP level increased twofold, 30 %, and threefold respectively. In this study, we have further demonstrated that the inhibition of the CHO cell growth was directly affected by high glucose concentration because it happened at both of high and low serum concentrations medium. The intracellular cAMP level regulates cell proliferation at high glucose growth condition in fibroblast cells. Therefore, the increase of cAMP might mediate the activation of Mitogen-activated Protein (MAP) kinase activity to inhibition of the CHO cells’ growth. In this study, the results showed that the MAP kinase phosphorylation did increase at high glucose concentration condition, and this activation was returned to the same level as grew in low glucose concentration when the cAMP signal was blocked. The high glucose concentration also regulated the CHO cell’s cell cycle during the G1 phase (0 to 8 hr growth). The intracellular cAMP level was increased and the phosphorylation of MAP kinase was postponed (or the dephosphorylation activity was inhibited) when glucose concentration was increased from 1 g/L to 10 g/L. Interestingly, the intracellular cAMP signals were blocked by cAMP dependent protein kinase A (PKA) inhibitor, and the MAP kinase phosphorylation activity as well as cell growth rate were returned to the same level as in low glucose concentration. Therefore, the results of these studies suggested that the high glucose might activate the MAP kinase activity by elevation of the intracellular cAMP level to inhibit the CHO cell growth.