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Western University

Cell and Developmental Biology

Reactive oxygen species

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The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams Jun 2022

The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams

Electronic Thesis and Dissertation Repository

B cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with recurrent mutations and high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine was tested for its ability to prolong lifespan of a mouse model of B-ALL and reduce frequency of mutations. Mice treated with 1g/L of N-acetylcysteine in drinking water were found to have delayed onset of B-ALL at 11 weeks of age and changes in gene expression relating to B cell development, calcium-apoptosis signaling, and pathways in cancer, although no differences in lifespan were observed. Tumours from treated …


Maternal Nicotine Exposure Induces Congenital Heart Defects In The Offspring Of Mice, Elizabeth Greco Jul 2019

Maternal Nicotine Exposure Induces Congenital Heart Defects In The Offspring Of Mice, Elizabeth Greco

Electronic Thesis and Dissertation Repository

Congenital heart defects are the most prevalent birth defect, and maternal cigarette smoking is a known risk factor. Nicotine replacement therapies are recommended to pregnant women who smoke to aid in smoking cessation, as this alternative is thought to be much safer compared to cigarette smoking. However, these products contain nicotine, and the safety of nicotine on the developing heart is not well known. In this thesis, a mouse model was used to test the hypothesis that maternal nicotine exposure (MNE) during pregnancy leads to congenital heart defects and coronary artery defects in the offspring of mice. MNE resulted in …


Pregestational Diabetes And Congenital Heart Defects: Role Of Reactive Oxygen Species, Hoda Moazzen Sep 2014

Pregestational Diabetes And Congenital Heart Defects: Role Of Reactive Oxygen Species, Hoda Moazzen

Electronic Thesis and Dissertation Repository

Women with pregestational diabetes are at a high risk of having babies with congenital heart defects (CHDs). The mechanisms of CHD induction in the offspring of women with pregestational diabetes remain elusive. With an ever-increasing rate of diabetes in young adults, there is a pressing need to understand the underlying mechanisms and initiate effective preventative strategies. The aim of this thesis is to study the role of reactive oxygen species (ROS) signalling in heart morphogenesis, unravel molecular mechanisms of CHDs induced by pregestational diabetes and provide new insights on potential therapeutic strategies. To this end, a mouse model of pregestational …


Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington Jun 2013

Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is characterized by deposition of the amyloid beta (Ab) peptide in the brain, an event which frequently but not universally correlates with nerve cell death. Although most nerve cells die in response to Ab, small populations of cells are able to survive by becoming resistant to Ab toxicity. Understanding the mechanisms by which cells become resistant to Ab may reveal novel treatments for AD. Interestingly, nerve cell lines selected for resistance against Ab exhibit increased glucose uptake and glycolytic flux. Here I show that these metabolic changes are mediated through an upregulation of pyruvate dehydrogenase kinase 1 …


The Effects Of Telomerase Inhibition On Cellular Senescence In Fetal Guinea Pig Muscle Cells, Stephanie E. Hallows Aug 2012

The Effects Of Telomerase Inhibition On Cellular Senescence In Fetal Guinea Pig Muscle Cells, Stephanie E. Hallows

Electronic Thesis and Dissertation Repository

Low birth weight infants have a higher risk of developing metabolic syndrome, including Type II Diabetes. Fetal muscle is growth restricted in low birth weight infants and is the main tissue for determining insulin resistance. Recent studies indicate premature senescence in low birth weight rodents, which could lead to adult disease. In utero environments may play a role in the development of senescence through increased reactive oxygen species (ROS). Telomerase is present at high levels during development and protects cells from cellular stress and apoptosis. We postulate that telomerase protects cells from DNA damage and premature senescence. A primary culture …


The Role Of Pex11-Beta In Peroxisome Biogenesis, Intracellular Relationship To Reactive Oxygen Species Levels And Redox-Sensitive Cell Signaling, Mark A. Fox Apr 2012

The Role Of Pex11-Beta In Peroxisome Biogenesis, Intracellular Relationship To Reactive Oxygen Species Levels And Redox-Sensitive Cell Signaling, Mark A. Fox

Electronic Thesis and Dissertation Repository

Peroxisomes are organelles whose roles in fatty acid metabolism and reactive oxygen species (ROS) elimination have contributed much attention in understanding their origin and biogenesis. Many studies have shown that de novo peroxisome biogenesis is an important regulatory process, while yeast studies suggest that total peroxisome numbers are in part regulated by proteins such as Pex11, which can facilitate the division of existing peroxisomes. Although de novo biogenesis and divisions are likely important mechanisms to peroxisome functioning, the regulation of peroxisome numbers during embryonic development is poorly understood. Peroxisome number and function are particularly crucial in oviparous animals such as …