Date of Award

2008

Publication Type

Master Thesis

Degree Name

M.Sc.

Department

Chemistry and Biochemistry

Keywords

Pure sciences, Biological sciences

Supervisor

S. Pandey

Rights

info:eu-repo/semantics/openAccess

Abstract

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. Working with NHFs, we have observed that quiescent fibroblasts, unlike dividing fibroblasts, do not undergo apoptosis when subjected to a high dose of external oxidative stress but become senescent instead. Our results have indicated that p21 and MnSOD over-expression in quiescent cells is highly correlated to resistance to external oxidative stress and senescence induction. Furthermore, we observed that fibroblasts harvested from individuals diagnosed with Alzheimer's disease have a higher amount of endogenous ROS and double stranded DNA breaks than NHFs, leading to an earlier onset of replicative senescence. Consistent with higher ROS levels, AD fibroblasts have up-regulated expression of MnSOD and decreased levels of non-selenium glutathione peroxidase.

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