Mechanisms responsible for the apoptosis of brain cells induced by glucose and serum deprivation: activation of apoptotic pathway

• Main Authors: Liao, YuanWen, 廖源文
• Other Authors: Chi-Mei Hsueh
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/53428806062588362003

碩士 === 國立中興大學 === 生物化學研究所 === 90 === Abstract The purpose of this thesis is to understand the mechanisms involved in the death of brain cells by glucose and serum deprivation. The effects of anoxia, aglycemia, and ischemia on the mixed brain cells were first analyzed. The damages caused by glucose with serum deprivation were further estimated and compare among various brain cells including neuron, astrocyte, microglia and mixed brain cells. Apoptotic pathways activated by the deprivation was also investigated the cells described above except microglia. We partially were interested in verifying the mitochondria-mediated cytochrome c-dependent apoptosis. Results showed that not only ischemia; anoxia and aglycemia all cause significant damages on the mixed brain cells. The damage caused by aglycemia was even more sever that at caused by ischemia or anoxia. Microglia, nevertheless, was the most venerable brain cells in respond to the glucose with deprivation (aglycemia). Results from western blotting analysis indicate that although mitochondria-mediated apoptosis was activated by glucose with serum deprivation in mixed brain cells, the same pathway was not induced in both neurons and astrocytes. Death receptor (or caspase-8)-mediated apoptosis on the other hand was responsible for the death of apoptotic pathway induced neuron. Despite the fact that the apoptotic pathway(s) trigged by glucose with serum deprivation activation of caspase-3 and inactivation of PARP appeared in all the cell types. These observations suggest a therapeutic role for caspase-3 inhibitor against aglycemia and/or ischemia.