Physiological Processes Commons^™

Alcohol And Metabolic Stress Synergize To Dysregulate Mitochondrial Health And Lipid Metabolism; Evidence From A Hepatocyte Spheroid Model, Eden M. Gallegos, Kaitlin Couvillion, Drake Darden, Keishla Rodriguez-Graciani, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease frequently co-occur, manifesting as MetALD. Understanding the hepatocyte-specific effects of alcohol and metabolic stressors is critical to uncovering mechanisms of synergistic injury. This study evaluated the individual and combined effects of ethanol, sugars, and saturated/monounsaturated fats on hepatocyte lipid metabolism, oxidative stress, and mitochondrial function using a 3D human HepaRG spheroid model. HepaRG spheroids were treated with ethanol (50 mm), sugar (glucose and fructose), and fatty acids alone or in combination for 10 d. The combination of ethanol (E) and metabolic (sugar and fat, SF) stressors (ESF) synergistically increased triglyceride content …

The Illusion Of Brain Health Across A Plastic Canvas, Thomas J. Kelly Jr, Lauren Gaspar, Jaime Ross Phd, Guiseppe Coppotelli Phd

Senior Honors Projects

In recent years, there has been increasing concern for the role that plastic waste, and more specifically micro- and nanoplastics, play in our environment and their potential health risks. Microplastics are particles less than 5 mm in size and nanoplastics are considered to be less than 1000 nm in size. Microplastics can either purposely be produced or can sludge off larger pieces of plastic. Microplastics have not only been detected within soil, air, and water, but have also recently been found to accumulate within the human body. The mosaic artwork that is presented in this project, entitled “Our Cerebral Plastic …

Skeletal And Dental Tissue Mineralization: The Potential Role Of The Endoplasmic Reticulum/Golgi Complex And The Endolysosomal And Autophagic Transport Systems, Irving M. Shapiro, Makarand V. Risbud, Tengteng Tang, William J. Landis

Department of Orthopaedic Surgery Faculty Papers

This paper presents a review of the potential role of the endoplasmic reticulum/Golgi complex and intracellular vesicles in mediating events leading to or associated with vertebrate tissue mineralization. The possible importance of these organelles in this process is suggested by observations that calcium ions accumulate in the tubules and lacunae of the endoplasmic reticulum and Golgi. Similar levels of calcium ions (approaching millimolar) are present in vesicles derived from endosomes, lysosomes and autophagosomes. The cellular level of phosphate ions in these organelles is also high (millimolar). While the source of these ions for mineral formation has not been identified, there …

Regulation Of Diabetic Cardiomyopathy Through Mitochondrial Import Of Long Non-Coding Rnas, Andrew Dodge Taylor

Graduate Theses, Dissertations, and Problem Reports (ETD)

Introduction: The leading cause of mortality in patients with diabetes mellitus is heart failure. When mitochondrial health and function is disrupted, cardiac contractile function is compromised. Therefore, understanding mitochondrial regulation may benefit predicting and countering diabetic cardiomyopathy. MicroRNAs (miRNAs) play a crucial role in diabetic cardiac mitochondrial protein expression. Long noncoding RNAs (lncRNAs) have been shown to regulate miRNAs, but not in the mitochondrion. Additionally, it has yet to be confirmed if lncRNAs utilize the same mechanisms for mitochondrial import that miRNAs use, or if lncRNA presence in the mitochondrion fluctuates in diabetic mitochondria like miRNA presence does. The …

Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …

Stromal Vascular Fraction Restores Vasodilatory Function By Reversing Mitochondrial Dysfunction And Oxidative Stress In Aging-Induced Coronary Microvascular Disease., Evan Paul Tracy

Electronic Theses and Dissertations

Background: Coronary Microvascular Disease (CMD) presents in aging post-menopausal women with chronic angina due to microvascular hyperconstriction. The objective was to identify mechanisms of adipose stromal vascular fraction’s (SVF) restorative effects on vasodilation. We hypothesize aging-induced CMD is caused by a) abrogated flow-mediated dilation (FMD) due to loss of nitric oxide signaling and b) ROS-dependent βADR desensitization & internalization, reversible by ameliorating mitochondrial dysfunction and oxidative stress with SVF. Methods: Coronary microvessels were isolated from female rats either young, old, or old with SVF tail-vein injection (OSVF). Pressure myography, RNA-sequencing, immunofluorescence, Western blotting, and morphological analysis were performed to …

The Role Of Calprotectin In T-Lymphocyte Driven Inflammation In A Mouse Model Of Psychological Trauma, Cassandra Moshfegh

Theses & Dissertations

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that affects nearly 45 million Americans. This mental disorder is characterized by behavioral symptoms such as learned helplessness, hyperarousal, withdrawal, and flashbacks. The deleterious effects of PTSD are far-reaching and go beyond behavioral dysfunction, as these individuals are at a three-fold higher risk of comorbid inflammatory diseases. Autonomic, metabolic, and cardiovascular diseases plague these individuals later in their lifetime, however, the mechanistic link connecting psychological trauma to this systemic peripheral immunological dysfunction remains elusive. T-lymphocyte-induced inflammation plays a significant role in all these disease pathologies. Previous work from our laboratory demonstrated …

Acute Oxygen-Sensing Via Mitochondria-Generated Temperature Transients In Rat Carotid Body Type I Cells, Ryan J. Rakoczy, Clay M. Schiebrel, Christopher N. Wyatt

Neuroscience, Cell Biology & Physiology Faculty Publications

The Carotid Bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Herein, preliminary evidence is presented supporting a novel oxygen-sensing hypothesis which suggests CB Type I cell “hypoxic signaling” may in part be mediated by mitochondria-generated thermal transients in TASK-channel-containing microdomains. Distances were measured between antibody-labeled mitochondria and TASK-potassium channels in primary rat CB Type I cells. Sub-micron distance measurements (TASK-1: 0.33 ± 0.04 µm, n = 47 vs TASK-3: 0.32 ± 0.03 µm, n = …

Measuring Mitochondrial Respiration In Vivo: From Mouse To Human, Arthur Orchanian, Brennan Schilling, Bruce Berkowitz Phd

Medical Student Research Symposium

Introduction: The mitochondrial energy ecosystem can be non-invasively interrogated in photoreceptors by combing a clinical tool, optical coherence tomography (OCT), with a mitochondrial protonophore (2,4 dinitrophenol, DNP). It remains unclear if only supra-clinical doses of DNP will be useful for mouse studies or if lower but clinically relevant doses of DNP would facilitate translation from mice to humans.

Methods: The experiment was a paired longitudinal design that took place over 2 days. On day 1, C57BL/6J mice were overnight dark adapted, then light-adapted for 5 h before OCT examination before regaining consciousness; a similar procedure was followed on day 2 …

Gender- And Region-Specific Changes In Estrogen Signaling In Aging Rat Brain Mitochondria, Christopher M. Evola, Tanner L. Hudson, Luping Huang, Adrian M. Corbett, Debra A. Mayes

Neuroscience, Cell Biology & Physiology Faculty Publications

Recently epidemiological studies suggest females lose neuroprotection from neurodegenerative diseases as they go through menopause. It has been hypothesized that this neuroprotection is hormone‐dependent. The current study characterized cell signaling molecules downstream of estrogen receptor beta that are known to play a role in memory, PKC, ERK, and connexin‐43, in regions of the brain associated with memory decline in an attempt to elucidate significant changes that occur post‐estrus. Total whole cell lysates were compared to isolated mitochondrial protein because mitochondrial function is known to be altered during aging. As hypothesized, protein concentrations differed depending on age, gender, and brain region. …

Determining The Effect Of Knocking Out Microrna-21 On Subsarcolemmal And Interfibrillar Mitochondria, Madhur Batra

Theses and Dissertations

Type 2 diabetes mellitus is a growing problem across the world and has significant pathological changes associated with it, including diabetic cardiomyopathy, wherein cardiac function is reduced. MicroRNA-21 has been shown to play a role in both the heart and diabetes so it was thought that knocking out miR-21 could have a protective effect on oxidative phosphorylation function in diabetic mice. Subsarcolemmal and interfibrillar mitochondria were isolated from adult male WT, miR-21 KO, db/db, and double knockout mice (db/db and miR-21 KO cross) and evaluated for function. Knocking out miR-21 in diabetic mice showed a restorative effect in Complex I …