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Cell and Developmental Biology

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Oxidative stress

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Nrf2 Regulation By Hsp90, Oxidation, And In Breast Cancer, Vy Ngo Mar 2021

Nrf2 Regulation By Hsp90, Oxidation, And In Breast Cancer, Vy Ngo

Electronic Thesis and Dissertation Repository

To cope with the dynamic range of stressful stimuli that a cell experiences within its lifetime, a host of adaptive cell survival and cell stress response pathways have evolved. The antioxidant and heat shock responses are two key cell stress response pathways primarily involved in the detoxification and elimination of oxidative stress and the maintenance of protein integrity, respectively. Traditionally, these responses are regarded and studied as two independent pathways. In this exploratory work, we hypothesize that oxidative damage to Nrf2 and Keap1 and their interactions with Hsp90 alter their function within the cellular antioxidant stress response. By establishing and …


Effect Of N-Acetyl-L-Cysteine Prevention Or Intervention On Diet Induced Beta Cell Compensation And Dysfunction, Madison Wallace Oct 2019

Effect Of N-Acetyl-L-Cysteine Prevention Or Intervention On Diet Induced Beta Cell Compensation And Dysfunction, Madison Wallace

Electronic Thesis and Dissertation Repository

Type 2 diabetes mellitus (T2DM) progression increases oxidative stress which contributes to beta cell compensation and eventual dysfunction. To investigate the role of antioxidant N-acetyl-L-cysteine (NAC) on beta cell function and pancreatic stellate cell activation (aSMA+) during early and late stages of compensation, NAC was used for preventative (p) and intervention (i) treatments in C57BL/6N mice fed a 60% kcal high-fat diet (HFD) for 8 or 22 weeks. Significantly improved glucose tolerance was observed at 22 weeks following pNAC treatment in HFD mice. Although 22-week HFD mice displayed hyperinsulinemia, beta cell hypertrophy, decreased beta cell PDX-1 nuclear localization, …


Alternative Splicing And Extra-Telomeric Role Of Telomerase Reverse Transcriptase Isoforms In Human Embryonic Stem Cells, Joohwan Kim May 2017

Alternative Splicing And Extra-Telomeric Role Of Telomerase Reverse Transcriptase Isoforms In Human Embryonic Stem Cells, Joohwan Kim

Electronic Thesis and Dissertation Repository

Human telomerase, a ribonucleoprotein complex consisting of a catalytic subunit (hTERT) and a RNA template component (TERC), prevents telomere attrition in human embryonic stem cells (hESCs) providing these cells with prolonged replicative capacity. Interestingly, hTERT has several alternatively spliced isoforms, most of which are catalytically inactive. One alternative splicing event involving a complete loss of exons 7 and 8 results in a catalytically inactive isoform called β-hTERT. The β-hTERT is highly expressed in certain cancer types and hESCs. Full-length hTERT (FL-hTERT) is known to translocate from nuclei to mitochondria when cells are exposed to either chronic (oxygen tension) or acute …


Maternal Nutrient Restriction In Pregnant Guinea Pigs Impacts Fetal-Placental Growth And Oxygenation, Alexander Elias Aug 2015

Maternal Nutrient Restriction In Pregnant Guinea Pigs Impacts Fetal-Placental Growth And Oxygenation, Alexander Elias

Electronic Thesis and Dissertation Repository

Maternal nutrient restriction (MNR) in guinea pigs results in placental structural abnormalities that reduce nutrient transport contributing to fetal growth restriction (FGR). However, whether fetal oxygenation is also reduced as a further mediator of altered growth and development remains unknown. Guinea pig sows were fed ad libitum (Controls) or 70% of the control diet pre-pregnant switching to 90% at mid-pregnancy (MNR). Animals were necropsied near term for fetal-placental growth measures, blood metabolites, and markers of tissue hypoxia and oxidative stress. MNR resulted in FGR with brains that are large and livers that are small relative to body weight which suggests …


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 …