Medicine and Health Sciences Commons^™

Cell-Free Dna Release During Programmed Cell Death In Kidney Ischemia Reperfusion Injury, Alexander Dionne

Electronic Thesis and Dissertation Repository

Transplantation is invariably associated with ischemia reperfusion injury (IRI) which causes organ dysfunction. IRI is also directly linked to several forms of programmed cell death including apoptosis and necroptosis, which increase kidney dysfunction, promote inflammation and may contribute to premature graft failure. The contribution of necroptosis and apoptosis following kidney IRI to cell-free DNA (cfDNA) generation and the potential of cfDNA to activate effectors such as NK cells involved in kidney IRI have not been defined. Our data indicate that necroptotic microvascular endothelial cells (MVECs) release considerably more cfDNA than apoptotic MVECs or untreated controls (p

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 …

Dynamic Light Scattering Optical Coherence Tomography To Probe Motion Of Subcellular Scatterers., Nico J J Arezza, Marjan Razani, Michael C Kolios

Medical Biophysics Publications

Optical coherence tomography (OCT) is used to provide anatomical information of biological systems but can also provide functional information by characterizing the motion of intracellular structures. Dynamic light scattering OCT was performed on intact, control MCF-7 breast cancer cells and cells either treated with paclitaxel to induce apoptosis or deprived of nutrients to induce oncosis. Autocorrelations (ACs) of the temporal fluctuations of OCT intensity signals demonstrate a significant decrease in decorrelation time after 24 h in both the paclitaxel-treated and nutrient-deprived cell groups but no significant differences between the two groups. The acquired ACs were then used as input for …

Protective Benefits Of Hydrogen Sulfide Treatment During Renal Transplantation, Ian Lobb

Electronic Thesis and Dissertation Repository

Ischemia/reperfusion injury (IRI) is inherent to renal transplantation (RTx) and is initiated when blood supply is necessarily removed during organ procurement (ischemia) and subsequently restored upon engraftment (reperfusion). During renal ischemia, ATP depletion causes tubular epithelial cell (TEC) injury and subsequent release of pro-inflammatory mediators. Upon reperfusion, influx of O₂ causes reactive oxygen species (ROS) production and infiltration of innate immune cells which release damaging ROS and proteases. Prolonged periods of IRI are associated with increased risk of delayed graft function (DGF) and decreased long-term graft survival. The endogenously produced gasotransmitter, hydrogen sulfide (H₂S), has recently been …

Mechanisms Of Atf4-Mediated Neuronal Apoptosis, Patrick Swan

Electronic Thesis and Dissertation Repository

Abstract to be provided

Timp3 Regulation Of Macrophage Activation And Apoptosis, Michael S. Brock

Electronic Thesis and Dissertation Repository

Acute respiratory distress syndrome (ARDS) is a lung disease involving profound inflammation. Origins of persistent inflammation in select cases of ARDS are poorly understood, and we propose persistent inflammatory macrophages may be one of its mechanisms. Macrophages polarize to either promote inflammation, or suppress inflammation. Tissue inhibitor of metalloproteinases 3 (TIMP3) reduces the pro-inflammatory polarization in macrophages. Additionally, studies have shown TIMP3 promotes apoptosis, and its absence delays recovery from bleomycin-induced lung injury.

We hypothesize that TIMP3 promotes apoptosis of murine macrophages through inhibition of metalloproteinase activity and stabilization of FAS on the cell surface. Pro-inflammatory Timp3^-/- bone marrow-derived …