Glucose 결핍시 유도되는 PI3K 의존적인 cytochrome C 방출과 caspase-9을 경유하는 apoptosis 경로

Abstract

Glucose metabolism is an essential process in maintaining the balance between life and death. Glucose depletion (GD) results in ATP depletion and this in turn triggers the death cascade. Severe ATP depletion usually leads to necrosis because ATP is required for many steps of apoptosis. Decreased glucose uptake and glycolysis result in oxidative stress and this alteration of the redox status in the cell triggers variable signal transduction pathways resulting in cell death. We previously observed that GD induced necrosis in A549 cells which was switched to apoptosis in the presence of antioxidant when reactive oxygen species (ROS) production is suppressed by catalase and N-acetyl-cysteine (NAC) in A549 cells. In this study, we investigated the relationship between phosphatidylinositol 3 kinase (PI3K) pathway and mitochondrial downstream death effectors, such as cytochrome C and caspase-3 and -9 in the GD-induced apoptotic pathway in A549 cells. PI3K inhibition decreased antioxidants/GD-induced apoptosis in A549 cells, and PI3K inhibitor LY294002 had inhibitory effect on antioxidants/GD-induced caspase-3 and, caspase-9 cleavage and PARP cleavage. LY294002 also reduced protein levels, phosphorylation, and nuclear translocation of p53 in A549 cells which are observed in the apoptotic condition. GD induces apoptosis through PI3K-dependent cytochrome C release and caspase-9 and -3 activation.