Studies of the cellular responses to thiamine deficiency in cortical neuron cells

• Main Authors: Shiang-Chin Chen, 陳香瑾
• Other Authors: Fung-Fang Wang
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/91856500593915104284

碩士 === 國立陽明大學 === 生物化學研究所 === 92 === Vitamin B1 (Thiamine) plays a critical role in energy and oxidative metabolism, its deficiency can result in abnormal oxidative degradation of nutrients. By treatment of cells with the thiamine antagonist amprolium as a means of inducing thiamine deficiency, we showed that thiamine deficiency elicited apoptosis in cultured cortical neuronal cells. The apoptosis was accompanied by the activation of caspases 3, 8, and 9 and a two-fold increase of reactive oxygen species (ROS) was detected. Treatment of cells with ROS inhibitors, NAC and vitamin C, did not prevent the amprolium induced death of neuronal cells. Western blot analysis using antibodies specific for phosphorylated MAP kinases demonstrated that amprolium treatment led to a decrease in the level of phosphorylated JNK and ERK. Exposure of cells to the JNK inhibitor SP600125, but not ERK inhibitor PD98059 and U0126, resulted in severe neuron death, suggesting that the activity of JNK is important to the survival of cortex neurons. The expression of p53 and its Ser-15 phosphorylation form was increased; and RT-PCR analysis indicated that the level of THTR-1, a p53 target gene, was upregulated. Mechanisms underlying the deficiency of vitamin B1 induced apoptosis remain to be determined.