Abstract HTML Views: 360 PDF Downloads: 139 Total Views/Downloads: 644
Abstract HTML Views: 218 PDF Downloads: 109 Total Views/Downloads: 440
In response to external oxidative stress/DNA damaging agents, mammalian cells may choose one of the
following pathways to avoid propagation of the damaged cells: repair the DNA and proceed with the normal cell cycle;
trigger apoptosis; or undergo senescence to block cell division. If these safeguard mechanisms fail, cells containing
damaged/mutated DNA will continue to propagate leading to cancer. Working with Human Diploid Fibroblasts, we have
observed that young quiescent fibroblasts, unlike dividing fibroblasts, do not undergo apoptosis when subjected to high
dose of external oxidative stress. Interestingly, when those quiescent fibroblasts are sub-cultured following H2O2
treatment, they display all the features of the senescent cell phenotype. Our results have indicated that p21 and MnSOD
over-expression in quiescent cells is highly correlated to resistance to oxidative stress and may induce senescence.
Moreover, there was no observable DNA damage in quiescent fibroblasts after 500 μM H2O2 treatment even though
oxidative damage to lipids and proteins was detected both before and after treatment. Most importantly, the mitochondrial
membrane potential in quiescent cells remained unchanged even after exposure to a high dose of external oxidative stress.
In dividing cells, Bcl-2 expression was down-regulated whereas Bax expression was up-regulated following oxidative
stress. On the other hand, Bcl-2 levels remained high and Bax was down-regulated in quiescent cells under identical
treatment. Our results reveal that the over-expression of p21 and Mn-SOD and the down-regulation of Bax in quiescent
cells could be responsible for their resistance against external oxidative stress and onset of senescence.