세포 노화과정에 있어서의 c-myb의 기능 = c-Myb mediated survival strategy of aging cells

다국어 초록 (Multilingual Abstract)

This study addressed the possibility that c-myb plays a role in ageing process as a molecular strategy for cell survival. Using in vitro ageing model system of cultured human diploid fibroblasts(HDF), the author confirmed previous reports that reactive oxygen species(ROS) accumulated in aged cells with increasing senescence-associated β-galactosidase during ageing. Using methyl thiazolyl tetrazolium(MTT) assay for cell viability, we demonstrated further that after being treated with H2O2, the cell viabilities of aged HDF(passage over 50) were much greater than those of young cells(passage under 20). The expression of stress proteins such as Hsp27, 60 and 70 did not change both in young and in aged cells after being treated with H2O2 while the displacement of Hsp60 from mitochondria to cytosol was greater in young than in aged cells. At the same time, the apoptosis-sensitive and stress-activated protein kinase/Jun N-terminal kinase(SAPK/JNK) activities were higher in young than in aged cells. The displacement of Hsp60 from mitochondria to cytosol was blocked when SAPK/JNK activation was inhibited. These findings imply that aged cells are more resistant to apoptosis through blocking the displacement of Hsp60 and SAPK/JNK activation.
In aged cells over 50 passages, the c-myb expression increased gradually with ageing and this increment was markedly influenced by oxidative stress, while young cells under 20 passages did not respond at all. To clarify the role of c-myb in oxidative stress, young cells under 20 passages which lacked c-myb expression were transfected with adenovirus-mediated c-myb to overexpress c-myb. These c-myb-overexpressed young cells survived well under oxidative stress as did aged cells. In addition, these c-myb-overexpressed young cells did not show SAPK/JNK activation, Hsp60 displacement and cytochrome C release as in aged cells. When the c-myb gene expression was suppressed by treatment with siRNA c-myb, even the aged cells showed a lowered cell viability and increased apoptosis as in young cells lacking c-myb expression. In conclusion, it is suggested that c-myb might act as a modulator of cell survival in ageing process by suppressing apoptosis in aged cells.

목차 (Table of Contents)

• 서 론 = 3
• 재료 및 방법 = 6
• 결 과 = 13
• 고 찰 = 32
• 요약 및 결론 = 40
• 참고문헌 = 42