Medicine and Health Sciences Commons^™

Junctophilin-2 Protects Cardiomyocytes Against Palmitate-Induced Injury, Xiaoyun Ji

Electronic Thesis and Dissertation Repository

Cardiac lipotoxicity may induce cardiomyocyte apoptosis, eventually leading to myocardial dysfunction and heart failure. This study investigated whether and how junctophilin-2 (JPH2) plays a role in palmitate-induced apoptosis in cardiomyocytes. Here, we found palmitate incubation reduced JPH2 protein levels, increased cytosolic Ca²⁺ and induced apoptosis in cardiomyocytes. JPH2 over-expression prevented the increased cytosolic Ca²⁺ and apoptosis in palmitate-stimulated cardiomyocytes. JPH2 over-expression also attenuated palmitate-induced CCAAT-enhancer-binding protein homologous protein (CHOP) expression and CHOP deletion alleviated palmitate-induced apoptosis. Furthermore, blocking Ca²⁺ release from ryanodine receptor-2 (RyR2) prevented palmitate-stimulated CHOP induction and apoptosis. Additionally, JPH2 silencing elevated cytosolic Ca^{2+ …}

The Role Of Atf4 In Amyloid-Beta-Induced Neuronal Death., Gillian Petroff

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is partially characterized by excessive accumulation of amyloid-b (Ab) in the brain. Ab oligomers have greater toxicity than Ab fibrils and induce neuronal stress. The Integrated Stress Response (ISR) is activated in response to cellular stress and increases expression of activating transcription factor 4 (ATF4) and its target genes. Prolonged activation has been shown to induce aberrant cell death, and increased markers of the ISR have been found in the brains of AD patients. However, the exact mechanism of amyloid-b-induced death is largely unknown. We aimed to determine if Ab-induced neuronal death occurs through ATF4-mediated upregulation of …

Caspases And Cancer: Connections Through Circular Dichroism Spectroscopy, Sarah M. Hethcox

Honors College Theses

While excessive cell death inevitably leads to negative effects, the endurance of damaged cells in the presence of death signals can be equally detrimental to health. Apoptosis, or programmed cell death, is a highly regulated process in which cues from within or from outside a cell can trigger an irreversible sequence of signals that carry out cell destruction known as the apoptotic cascade. A group of enzymes called caspases play a vital role in this cascade with some participating as initiators and others acting as effectors of protein cleavage and intracellular breakdown. Although it is normal for the activity of …

Role Of Atm In T Cell Dysfunction During Chronic Viral Infections, Juan Zhao

Electronic Theses and Dissertations

Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection leads to a phenomenon of inflammaging, in which chronic infection or inflammation induces an immune aged phenotype with T cell dysfunction. Thus, HCV or HIV infection has been deemed as a model to study the mechanisms of T cell infammaging and viral persistence in humans. In this dissertation, T cell homeostasis, DNA damage and repair machineries were investigated in patients with chronic HCV or HIV infection at risk for inflammaging. We found a significant depletion in CD4 T cells, which was correlated with their apoptosis in chronically HCV/HIVinfected patients, compared …

An In Vitro And In Vivo Evaluation Of The Anticancer Potential Of Resveratrol And Pterostilbene Against Hpv-E6 Positive Cancers, Kaushiki Chatterjee

Dissertations, Theses, and Capstone Projects

Cervical cancer remains as one of the most prevalent cancers effecting women globally. Lack of awareness and affordable prophylactic and therapeutic options in developing countries drive the need for alternative low-cost approaches. Dietary polyphenols have gained increased attention as possible anti-cancer agents. Our study aims to investigate whether two natural structural analogs, resveratrol and pterostilbene, exhibit anti-HPV (Human papillomavirus) activity in cervical cancer. To determine the efficacy of these polyphenols, extensive in vitro and in vivo analyses were carried out. For the in vitro studies we utilized human HeLa cells (HPV18 positive) and murine TC1 cells (HPV 16 oncogene positive). …

Senecavirus A: Pathogenicity And Interactions With Host Cell Death Pathway, Maureen Hoch Vieira Fernandes

Electronic Theses and Dissertations

Senecavirus A (SVA) is a positive sense single-strand RNA virus of the genus Senecavirus, family Picornaviridae. Senecavirus A is an emerging picornavirus of swine, which causes vesicular disease (VD) in pigs that is clinically indistinguishable from footand- mouth disease and other high consequence VDs of swine. There is evidence that SVA has been circulating in the US swine population since the late eighty’s, however, recently the virus emerged worldwide, and it has been associated with several VD outbreaks in pigs in many of the major swine producing countries. Despite the recent surge in the number of cases of …

Using Peptide Mimetics To Probe Protein-Protein Interactions Significant In Cancers, Robert H. Whitaker

All ETDs from UAB

Protein-protein interactions are critical for cell life. One aspect of cellular regulation where such protein-protein interactions occur is in the highly regulated process of programmed cell death (or apoptosis). Apoptosis is critical for normal tissue homeostasis, differentiation, and if dysregulated is a driver of disease including cancers. At the center of apoptotic regulation is the BCL2 protein family whose intra-familial protein-protein interactions balance cell stress signaling either allowing the cell to survive or inducing mitochondrial cell death. These BCL2 protein interactions are accomplished through the BH3 motif. While unique to the BCL2 family, a similar motif, the reverse BH3, has …

The Effects Of Obesity, Chronic Stress, And Exercise On Pancreatic Health, Abigail Tice

Graduate Theses, Dissertations, and Problem Reports

Obesity is concomitant with hyperglycemic conditions, increased proinflammatory cytokines, and increased oxidative stress. Under hyperglycemia, thioredoxin interacting protein (TXNIP) is increased and causes increased oxidative stress and pancreatic b-cell apoptosis. Chronic stress is associated with increased glucocorticoid levels and a proinflammatory environment. The purpose of this study was to examine the effects of obesity, chronic stress, and exercise on pancreatic health.

Lean Zucker Rats (LZRs) and Obese Zucker Rats (OZRs) were randomly assigned to four groups: 1) sedentary controls (C: n=8 per); 2) unpredictable chronic mild stress (UCMS) (S: n=8); 3) exercise (E: n=8); and 4) combined UCMS and exercise …