Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by a significant increase in neuronal loss. Cell death is the fate of neurons when exposed to stress that exceeds its capacity to recover. Oxidative stress (OS) plays a significant role on neuronal damage. Reactive oxygen species (ROS) generated from agents such as hydrogen peroxide (H2O2) leads to cell damage and reduction of cell viability. Sirtuin 1 (SIRT1) is a therapeutic target for neurodegenerative disorders because it regulates several cellular functions and biological processes that promote cellular longevity.
The aim of this study was to examine the role of SRT1720 in protecting cells from H2O2 induced stress in Ntera 2/cl.D1(NT2) cells. NT2 is a human teratocarcinoma cell line which has been proven to be a useful in vitro system for the investigation of functions related to human neuronal and glial systems.
The results illustrated that H2O2 significantly reduced cell viability in a time and concentration dependent manner. Moreover, pre-treatment with low concentrations of SRT1720 for 48 hours protected against the effects of H2O2. Also, a combination of H2O2 and SRT1720 improved cell viability. Interestingly, apoptotic or necrotic cell death was not detected after H2O2 treatment in the cell culture model system employed.
Future studies aimed at investigating the effects of H2O2 on the integrity of the mitochondrial membrane (mitochondrial potential and mitochondrial metabolic activity) and glutathione peroxidase (GPx) may shed light on its mechanism of action in NT2 cells. In addition, investigating the mechanism of SRT1720 at the mitochondrial level such as PGC-1α to understand how it exerts a protective role against oxidative stress induced by H2O2 is warranted.
|Advisor:||Tejani-Butt, Shanaz M|
|Commitee:||Tejani-Butt, Shanaz M, Tchao, Ruy, Peethambaran, Bela|
|School:||University of the Sciences in Philadelphia|
|Department:||Pharmacology & Toxicology|
|School Location:||United States -- Pennsylvania|
|Source:||MAI 81/11(E), Masters Abstracts International|
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