(The) effects of anti cancer drug induced oxidative stress on the alpha 1 subunit degradation of AMPK complex

다국어 초록 (Multilingual Abstract)

The 5’-AMP- activated protein kinase (AMPK) functions as a metabolic fuel gauge that is activated in response to numerous environmental stressors to restore cellular and whole body energy balance. We show the regulation of AMPK α in the cell cycle by the increased ROS level in a cell damaged condition and we discovered that the total protein level of AMPK α is decreased by H2O2 treatment in the cell, but the activity of AMPK α is increased. Because the decreased of AMPK α is rescued by MG 132 treatment, we know that the AMPK α is degraded by proteasome pathway. Also, We attempted that the ubiquitination of AMPK α using immunoprecipitation assay. The poly-ubiquitination of AMPK α is dramatically increased in H2O2 treatment than non-treatment. Interestingly, the degradation rate of AMPK α1 is more decreased than the rate AMPK α2 in respond to H2O2. These facts are possible that the AMPK α2 escape from the proteasome target though the AMPK α2 increased activity is trans-localized to nucleus. Although increased activity of AMPK α by H2O2 is possible that is influence in cell cycle regulation thought directly phosphorylated p53. We don’t know the increased phosphor-p53 whether p53 dependant cell death or not the survival thought cell cycle arrest, yet. Particularly, high cell density in the physiologic condition of increased ROS level is similar result in H2O2 treatment condition. We show that total AMPK α1 is decreased by normal and cancer cell lines.

목차 (Table of Contents)

• Abstract 1
• Introduction 2
• Materials and Methods 5
• Results 8
• Figure 12
• Discussion 21
• References 22