c-myb has a character of oxidative stress resistance in aged human diploid fibroblasts: regulates SAPK/JNK and Hsp60 pathway consequently.

ABSTRACT

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.