Heat Shock and Ceramide Have Different Apoptotic Pathways

다국어 초록 (Multilingual Abstract)

Heat shock stresses induce the apoptotic cell death. Recently, ceramide produced during heat shock was proposed to mediate apoptosis. To determine whether the apoptosis induced by heat shock and ceramide have common apoptotic pathway, we examine the cellular responses in radiation induced fibrosarcoma(RIF-1) cell line and thermotolerant cell line(TR-RIF-1) by C2-ceramide and heat shock. When both cells were exposed to heat shock and ceramide, they responded differently in terms of survivals of cells, amounts of apoptosis, and morphological changes. TR-RIF-1 protected the heat induced apoptosis, but was more sensitive to ceramide induced apoptosis than RIF-1. To explain this physiological difference, biochemical changes of cells exposed to heat and ceramide were compared. When cells were exposed to the heat shock, cellular protein synthesis was stopped immediately, and then heat shock protein(hsp) synthesis appeared in 4-12 h depending on the amount of stress. However, when cells were exposed to ceramide, blockage of protein synthesis and heat shock protein synthesis were not detected. Simultaneously, we found that stress-activated protein kinase/c-Jun N-terminal kinase(SAPK/JNK) and caspase-3 activity were more dramatically activated immediately after heat shock than after ceramide treatment. Our results suggest that heat shock and C2-ceramide have different apoptotic signal pathway or have different molecules to regulate the pathways. The further studies are performing to find out the upstream of above signals by measuring membrane lipid peroxidation and reactive oxygen species in apoptotic cells.