c-myb has a character of oxidative stress resistance in aged human diploid fibroblasts: regulates SAPK/JNK and Hsp60 pathway consequently.
This study examined whether c-myb acts as a survival molecule in aged cells. A previous in vitro ageing model suggested that aged cells have a higher cell capacity for survival after exposure to oxidative stress, which involves blockage of the translocation of Hsp60 from the mitochondria to the cytoplasm followed by SAPK/JNK inactivation, than young cells. In human diploid fibroblasts (HDFs), c-myb expression increased gradually with ageing, and this increase had a significant influence on the cell survival capacity after exposure to oxidative stress. To clarify the role of c-myb in oxidative stress, young cells under 21 passages, which lacked c-myb expression, were transfected with adenovirus-mediated c-myb for express c-myb. These c-myb-over-expressed young cells showed increased cell viability upon exposure to oxidative stress to a similar extent to that of the aged cells. In addition, these c-myb-over-expressed young cells did not exhibit SAPK/JNK activation, Hsp60 displacement and cytochrome C release, as was observed in aged cells. The aged cells that had c-myb suppressed using siRNA c-myb showed reduced cell viability and increased apoptosis in a manner to that observed in young cells. From this study, c-myb blocked SAPK/JNK and Hsp60 translocation upon exposure to oxidative stress. This result suggests that c-myb might act as a modulator of cell survival in the ageing process by suppressing apoptosis in aged cells.
Lee
Young-Hee
YH
Department of Oral Biochemistry and Institute of Oral-Bio Science, BK21 program, School of Dentistry, Chonbuk National University, Jeonju, Jeonbuk, 561-712, Korea.
Lee
Nan-Hee
NH
Bhattarai
Govinda
G
Hwang
Pyong-Han
PH
Kim
Tae-Il
TI
Jhee
Eun-Chung
EC
Yi
Ho-Keun
HK
D000375:Aging / Q000378:metabolism*; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000378:metabolism*; D004171:Diploidy; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D034741:RNA, Small Interfering
D018834:Chaperonin 60; D020598:Proto-Oncogene Proteins c-myb; D034741:RNA, Small Interfering; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4