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Articles 1 - 15 of 15
Full-Text Articles in Life Sciences
Acetylation Regulates Thioredoxin Reductase Activity And Oligomerization, David E. Wright
Acetylation Regulates Thioredoxin Reductase Activity And Oligomerization, David E. Wright
Electronic Thesis and Dissertation Repository
The Thioredoxin (Trx) system provides the cell with robust defense against oxidative stress and regulates the function of nearly every cellular process through the reduction-oxidation (redox) regulation of proteins. The Trx system is involved in the development of many diseases ranging from cancer to cardiovascular disorders. Thioredoxin reductase (TrxR) is the key enzyme in the Trx system and contains the 21st genetically encoded amino acid, selenocysteine (Sec). There were multiple experimentally identified TrxR acetylation sites with an unknown effect on TrxR activity. My thesis tested the hypothesis that programmed protein acetylation will enhance the activity of TrxR1. I used …
Characterizing The Structural, Biophysical And Functional Effects Of S-Glutathionylation On Stim1 Ca2+ Sensing, Christian Michael Sirko
Characterizing The Structural, Biophysical And Functional Effects Of S-Glutathionylation On Stim1 Ca2+ Sensing, Christian Michael Sirko
Electronic Thesis and Dissertation Repository
Stromal interaction molecule 1 (STIM1) is an endo/sarcoplasmic reticulum (ER/SR) calcium (Ca2+) sensing protein that initiates cytoplasmic Ca2+ influx via store-operated calcium entry (SOCE). STIM1, in conjunction with Orai, a plasma membrane (PM) protein, function as mediators of SOCE through the formation of calcium-release activated calcium (CRAC) channels. S-Glutathionylation of STIM1 at Cys56 has been shown to evoke constitutive Ca2+ entry in DT40 cells, however no studies have carefully investigated the biophysical and structural effects of this covalent modification to the luminal domain, which are critical for understanding the molecular mechanism underlying the regulation of …
Nrf2 Regulation By Hsp90, Oxidation, And In Breast Cancer, Vy Ngo
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
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, …
Investigating The Protective Effects Of Telomerase Reverse Transcriptase On Neuronal Metabolism And Resistance To Amyloid-Beta, Olivia Singh
Investigating The Protective Effects Of Telomerase Reverse Transcriptase On Neuronal Metabolism And Resistance To Amyloid-Beta, Olivia Singh
Electronic Thesis and Dissertation Repository
Maintenance of telomere length during cell division is dependent on the catalytic subunit telomerase reverse transcriptase (TERT), which adds TTAGGG repeats to the ends of chromosomes to prevent telomere shortening during DNA replication. However, non-telomeric roles of TERT have emerged under oxidative stress whereby TERT translocates from the nucleus to the mitochondria and protects against mitochondrial dysfunction through a poorly defined mechanism. A major pathological feature of Alzheimer’s Disease (AD) is the progressive accumulation of amyloid-beta (Aβ) peptide within the cortex and hippocampus. Aβ can directly interfere with mitochondrial respiration and promote mitochondrial dysfunction, ROS production, and neuronal cell death. …
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 …
The Long Haul: Migratory Flight Preparation And Performance In Songbirds, Morag F. Dick
The Long Haul: Migratory Flight Preparation And Performance In Songbirds, Morag F. Dick
Electronic Thesis and Dissertation Repository
Migration requires birds to sustain high intensity endurance exercise for periods lasting from hours to days. Similar to athletes, preparation and nutrition is key to success. Birds seasonally prepare for migration, which includes increasing the capacity to oxidize fat in the flight muscles. Beyond fuelling migration, n-3 long-chain polyunsaturated fatty acids (PUFA) are hypothesized to be natural doping agents and increase endurance and fatty acid oxidative capacity. I examined how birds prepare for and sustain migratory flight and directly tested the role of n-3 PUFA. Using yellow-rumped warblers (Setophaga coronata) as a model species, I first examined the …
Parkin Misfolding, Dysfunction, And Degradation In Parkinson's Disease, Alexander S. Mccarton
Parkin Misfolding, Dysfunction, And Degradation In Parkinson's Disease, Alexander S. Mccarton
Electronic Thesis and Dissertation Repository
Mutations in the gene encoding parkin (PARK2) result in familial early onset forms of Parkinson’s disease (PD) based on the loss of parkin’s E3 ubiquitin ligase function. Protein misfolding is a common molecular feature of most neurodegenerative diseases, including PD. To test whether parkin misfolding also plays a role in the more common spontaneous PD, we established and functionally characterized a parkin yeast model. We found that oxidative and protein folding stress, parkin point mutations and truncations, and parkin’s interaction with the PD-associated kinase PINK1 profoundly alter parkin’s subcellular localization and toxicity. Notably, these conditions also induce parkin fragmentation, degradation, …
Co-Morbidity Of Alzheimer’S Disease And Stroke: Cognitive Deficits And Cellular Pathologies In Two Co-Morbid Animal Models, Jennifer L. Au
Co-Morbidity Of Alzheimer’S Disease And Stroke: Cognitive Deficits And Cellular Pathologies In Two Co-Morbid Animal Models, Jennifer L. Au
Electronic Thesis and Dissertation Repository
Prior to beta-amyloid (Aβ) protein accumulation into plaques in Alzheimer’s disease (AD), neuroinflammation and oxidative stress have been shown to contribute to early cognitive decline. These cellular pathologies are coincident in stroke, which is considered a risk factor for AD. This study investigated the co-morbid effects of AD and stroke on behavioural and cellular pathology in two rodent models. Motor function, memory and microglial neuroinflammation were investigated in a stroke and Aβ injection model and mutant human amyloid precursor protein (APP) transgenic model with stroke. Injections of endothelin-1 into the right striatum were used to model stroke and AD was …
Maternal Nutrient Restriction In Pregnant Guinea Pigs Impacts Fetal-Placental Growth And Oxygenation, Alexander Elias
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 …
Nicotinamide Riboside Delivery Generates Nad+ Reserves To Protect Vascular Cells Against Oxidative Damage, Krista M. Hawrylyshyn
Nicotinamide Riboside Delivery Generates Nad+ Reserves To Protect Vascular Cells Against Oxidative Damage, Krista M. Hawrylyshyn
Electronic Thesis and Dissertation Repository
The ability of vascular cells to withstand oxidative insults is critical to vascular health. NAD+, which drives poly (ADP-ribose) polymerase (PARP) and sirtuin (SIRT) reactions, can be compromised and strategies for overcoming this limitation in the vasculature do not exist. This study determines if nicotinamide riboside (NR) delivery can augment NAD+ stores and fuel resistance to oxidative stress. I established that oxidative-stress insult on vascular cells decreased NAD+ levels, accompanied by a striking increase in nuclear PAR-chain accumulation. PARP inhibition abolished PAR-chain formation and preserved NAD+ levels, establishing PARP in NAD+ consumption in this …
Pregestational Diabetes And Congenital Heart Defects: Role Of Reactive Oxygen Species, Hoda Moazzen
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 …
Mechanistics Of Prothymosin Alpha And Nrf2 In The Keap1-Nrf2 Mediated Oxidative Stress Response, Halema Khan
Mechanistics Of Prothymosin Alpha And Nrf2 In The Keap1-Nrf2 Mediated Oxidative Stress Response, Halema Khan
Electronic Thesis and Dissertation Repository
In an effort to dissect the mechanism of interaction of IDPs, in this thesis we focus on Prothymosin a (ProTa) and nuclear factor erythroid 2-related factor 2 (Nrf2), intrinsically disordered proteins, in the Nrf2 mediated oxidative stress response. Kelch-like ECH-associated protein 1 (Keap1) is an inhibitor of Nrf2, a key transcription factor of cytoprotective genes. Under unstressed conditions, Keap1 interacts with Nrf2 in the cytoplasm via its Kelch domain and suppresses Nrf2 activity. During oxidative stress, Nrf2 is released from Keap1 and is shuttled to the nucleus, where it initiates pro cell survival gene transcription. ProTa also interacts with the …
Investigating The Pathological Response To Beta Amyloid Toxicity In Rats: The Role Of Age And The Antioxidant Catalase-Skl, Hayley J. Nell
Investigating The Pathological Response To Beta Amyloid Toxicity In Rats: The Role Of Age And The Antioxidant Catalase-Skl, Hayley J. Nell
Electronic Thesis and Dissertation Repository
Accumulation of beta-amyloid (Aβ) in the brain is a major contributor to the cellular pathology and cognitive impairment observed in Alzheimer’s disease (AD). In part, Aβ exerts its toxic effects by increasing reactive oxygen species (ROS) and neuroinflammation in the brain. Aging, a major risk factor for AD is also associated with increased production of ROS. This study investigated the age-related pathological response to Aβ toxicity and examined whether catalase-SKL(CAT-SKL), a genetically engineered derivative of the peroxisomal antioxidant enzyme catalase, is able to reduce Aβ toxicity. Bilateral intracerebroventricular (icv) injections of the Aβ25-35 peptide was used to model Aβ …
Trace Metal Limitation And Its Role In Oxidative Stress Of Coral Algal Symbionts; Implications For Thermally Induced Coral Bleaching Events., Katrina Lynn Iglic
Trace Metal Limitation And Its Role In Oxidative Stress Of Coral Algal Symbionts; Implications For Thermally Induced Coral Bleaching Events., Katrina Lynn Iglic
Electronic Thesis and Dissertation Repository
Coral bleaching, the process in which corals expel their photosynthetic symbionts (Genus Symbiodinium), is caused by high temperature and irradiance stress. The synergistic effect of each stressor is the generation of damaging reactive oxygen and nitrogen species (ROS and RNS), which are normally mitigated physiologically by antioxidant enzyme activity. Antioxidant enzymes require iron, copper, manganese and zinc in their structure and the limited nature of these trace metals in reef environments may enhance ROS production under elevated temperature and irradiance. The hypothesis tested within this thesis was that a limited availability of the trace metals Fe, Mn, Cu and …