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

Biogerontology. 2010 Jun;11(3):267-74. doi: 10.1007/s10522-009-9244-0. Epub 2009 Aug 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Apoptosis
  • Base Sequence
  • Blotting, Western
  • Cells, Cultured
  • Chaperonin 60 / metabolism*
  • Diploidy*
  • Fibroblasts / metabolism
  • Humans
  • MAP Kinase Kinase 4 / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Oxidative Stress*
  • Proto-Oncogene Proteins c-myb / metabolism*
  • RNA, Small Interfering

Substances

  • Chaperonin 60
  • Proto-Oncogene Proteins c-myb
  • RNA, Small Interfering
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4