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Full-Text Articles in Medicine and Health Sciences
The Role Of Mitochondrial Genetic Background In Cellular Function, Response To Cell Stress And Disease Susceptability, Jamelle A. Brown
The Role Of Mitochondrial Genetic Background In Cellular Function, Response To Cell Stress And Disease Susceptability, Jamelle A. Brown
All ETDs from UAB
There is a differential susceptibility associated with several diseases including cardiovascular disease (CVD) and hypertension, with Blacks being more likely to develop these conditions. Blacks are also more likely to die from these diseases. To explain the genetic etiology underlying CVD pathogenesis, the primary focus has been on nuclear genetics-environmental interactions, whereas the contribution of mitochondrial genetics is less explored. Therefore, we sought to determine whether differences exist in cellular function and response to cell stress in healthy and diseased individuals with distinct mitochondrial genetic backgrounds. To determine this, we sought first to develop a technique to detect and quantify …
The Role Of Protein O-Glcnacylation In Regulating Mitochondrial Function, Jalessa Nicole Wright
The Role Of Protein O-Glcnacylation In Regulating Mitochondrial Function, Jalessa Nicole Wright
All ETDs from UAB
The attachment of O-linked-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins has emerged as an important regulatory mechanism in transcriptional regulation, protein activation as well as cell survival. Several studies have reported that elevated O-GlcNAc levels have adverse effects on mitochondrial function. These negative effects have been linked to O-GlcNAc modification of mitochondrial proteins that are integral across multiple metabolic cell processes i.e. VDAC, NDUFA9 and DRP-1. Mitochondrial complexes I, III and IV all contain subunit proteins that are O-GlcNAc modified and increased O-GlcNAcylation of these proteins is associated with deficits in oxidative phosphorylation in these models. Conversely, it has …
Activation Of Ampk To Diminish Sepsis-Induced Lung Injury, Nathaniel Bone
Activation Of Ampk To Diminish Sepsis-Induced Lung Injury, Nathaniel Bone
All ETDs from UAB
Sepsis is the most frequent cause of death of hospitalized patients in modern ICUs. Severe infection, trauma, hemorrhage, burns, and surgery are significant causes of multi-organ injury and immune dysfunction that in turn primes for a high risk of secondary lung infections. In addition to detrimental inflammation, sepsis is linked to loss of metabolic plasticity due to mitochondrial dysfunction in immune cells and lung tissue. In particular, mitochondrial failure in lungs of critically ill septic patients is correlated with high mortality rates. We proposed that AMP-activated protein kinase (AMPK) activation, a major bioenergetic sensor and metabolic regulator, is a plausible …
Autophagy In Mitochondrial Quality Control And Proteotoxicity In Neurons, Matthew Redmann
Autophagy In Mitochondrial Quality Control And Proteotoxicity In Neurons, Matthew Redmann
All ETDs from UAB
Parkinson’s disease (PD) is the 2nd most common neurodegenerative disorder with aging as a significant risk factor. Sharing with aging brains, postmortem PD brains exhibit cellular deficits including autophagic dysfunction, mitochondrial dysfunction, and intracellular protein aggregates of alpha-synuclein. This dissertation will focus on the interplay between these key disease features. To that end, we coupled primary cortical neuronal cultures from either rats or mice with Seahorse extracellular flux, metabolomics and biochemical techniques. Autophagy is an important cell recycling program responsible for the clearance of damaged proteins and organelles. Bafilomycin A1 and chloroquine are compounds that inhibit autophagy by targeting the …
Mitochondrial Genetics And Cellular Metabolism Regulate Tumorigenicity And Metastatic Potential, Kyle Paul Feeley
Mitochondrial Genetics And Cellular Metabolism Regulate Tumorigenicity And Metastatic Potential, Kyle Paul Feeley
All ETDs from UAB
Current paradigms of carcinogenic risk suggest that genetic, hormonal, and environmental factors combine to influence an individual's predilection for breast cancer and related metastatic tumor formation. The genetic component, in particular, has become the focus of many emergent studies. A renewed focus on cancer metabolism and the Warburg effect has similarly cast a spotlight on the role, if any, of the mitochondrion in directing disease progression. Analysis of the direct contribution of mitochondrial DNA on tumorigenicity is made possible through the use of mitochondrial-nuclear exchange (MNX) mice in which nuclei from normal FVB mice (the background strain of the tg: …
Mitochondrial Morphology And Function In Neuronal Cells Under Stress, Lonnie Schneider
Mitochondrial Morphology And Function In Neuronal Cells Under Stress, Lonnie Schneider
All ETDs from UAB
Neurodegenerative disease encompasses a wide range of conditions and pathologies that can manifest at any age depending on the etiology. A major factor in both early onset and age-related neurodegeneration is mitochondrial dysfunction. To investigate how mitochondrial bioenergetics is affected by cellular stress, we used an in vitro culture system to examine mitochondrial function in response to oxidative stress. We also studied an in vivo model of neuronal ceroid lipofuscinosis to determine the impact of deficient autophagy-lysosomal activity on mitochondrial morphology, composition and function. In vitro we found that retinoic acid-induced differentiation of dopaminergic neuroblastoma SH-SY5Y cells exhibited increased mitochondrial …
Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L Fetterman Brenneman
Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L Fetterman Brenneman
All ETDs from UAB
While progress has been made in understanding the development and progression of cardiovascular disease (CVD), the mechanisms of CVD risk and initiation are not completely understood. It is widely accepted that CVD is the result of a combination of genetic and environmental factors but it is not known why some populations with otherwise similar risk factors appear more susceptible to CVD than others. It is also known that different strains of laboratory mice have distinct susceptibilities to CVD development. For example, C3H mice are resistant to diet induced atherogenesis whereas C57 animals are susceptible. We have also found that the …
Regulation Of Vascular Smooth Muscle Cell Signaling And Metabolism By Platelet-Derived Growth Factor, Jessica Perez
Regulation Of Vascular Smooth Muscle Cell Signaling And Metabolism By Platelet-Derived Growth Factor, Jessica Perez
All ETDs from UAB
Growth factors are important inducers of vascular cell growth whose regulation is altered during the pathogenesis of atherosclerosis. An increase in growth factor and cytokine production, as well as lipid oxidation is observed in cardiovascular disease (CVD) and contributes to altered vascular cell signaling, exacerbated atherosclerotic lesions and heart failure. A change in cellular bioenergetic status due to mitochondrial dysfunction or damage has also been noted in CVD. In this thesis, we first examine cell signaling pathways in vascular smooth muscle cells (VSMC) which are activated in response to platelet-derived growth factor (PDGF) and regulate the cell cycle protein changes …