Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 10 of 10
Full-Text Articles in Medicine and Health Sciences
Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal
Electronic Theses and Dissertations
Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …
Role Of Atm In T Cell Dysfunction During Chronic Viral Infections, Juan Zhao
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 …
Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton
Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton
Electronic Theses and Dissertations
Endogenous and exogenous agents that can damage DNA are a constant threat to genome stability in all living cells. In response, cells have evolved an array of mechanisms to repair DNA damage or to eliminate the cells damaged beyond repair. One of these mechanisms is nucleotide excision repair (NER) which is the major repair pathway responsible for removing a wide variety of bulky DNA lesions. Deficiency, or mutation, in one or several of the NER repair proteins is responsible for many diseases, including cancer. Prokaryotic NER involves only three proteins to recognize and incise a damaged site, while eukaryotic NER …
Distinct Domains Of Bax Are Involved In Mitochondrial Bioenergetics And Apoptosis, Ge Zhang
Distinct Domains Of Bax Are Involved In Mitochondrial Bioenergetics And Apoptosis, Ge Zhang
Electronic Theses and Dissertations
Apoptosis is essential for cellular homeostasis and is also a pathologic feature of various diseases. The balance between Bcl-2 family proteins determines whether a cell will live or die. Bax, a member of the BCL-2 family proteins, is a pro-apoptotic protein that exists in both a soluble, cytoplasmic form and a membrane-bound form. Upon apoptotic stimuli, Bax undergoes a conformational change and translocates to the mitochondria, initiating apoptotic events. However, little is known about whether Bax is involved in the regulation of mitochondrial function under non-apoptotic conditions, and how Bax binds to mitochondria to exert its activity. Here, we investigate …
Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass
Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass
Electronic Theses and Dissertations
Transplanted embryonic stem (ES) cells following myocardial infarction (MI) contribute to limited cardiac repair and regeneration with improved function. Therefore novel strategies are still needed to enhance the efficacy by which ES cells differentiate into cardiac cell types and inhibit adverse remodeling in the infarcted myocardium. Our studies evaluate whether genetic manipulation of transplanted ES cells employing miR- 1, a pro-cardiac microRNA, and TIMP-1, an anti-apoptotic and anti-fibrotic protein, will enhance cardiac myocyte differentiation, inhibit native cardiac apoptosis, and reduce fibrosis in the infarcted myocardium. Furthermore, we assess levels of associated pro- (caspase-3, PTEN) and anti-(Akt) apoptotic proteins as well …
Studies On A Novel Human Cardiospecific Transcription Factor And Its Involvement In Omi/Htra2 Mediated Cell Death, Meenakshi Puthucode Balakrishnan
Studies On A Novel Human Cardiospecific Transcription Factor And Its Involvement In Omi/Htra2 Mediated Cell Death, Meenakshi Puthucode Balakrishnan
Electronic Theses and Dissertations
Omi/HtrA2 is a mitochondrial serine protease that is known to translocate to the cytoplasm upon induction of apoptosis and to activate caspase-dependent and caspase-independent cell death. The molecular mechanism of Omi/HtrA2's function is not clear but involves degradation of specific substrates. These substrates include cytoplasmic, mitochondrial, as well as nuclear proteins. We have isolated a new Omi/HtrA2 interactor, the THAP5 protein. THAP5 is a fifth member of a large family of transcription factors that are involved in cell proliferation, apoptosis, cell cycle control, chromosome segregation, chromatin modification and transcriptional regulation. THAP5 is an approximately 50kDa nuclear protein, with a restricted …
Transplantation Of Ips Cells Reduces Apoptosis And Fibrosis And Improves Cardiac Function In Streptozotocin-Induced Diabetic Rats, Sarah Elizabeth Neel
Transplantation Of Ips Cells Reduces Apoptosis And Fibrosis And Improves Cardiac Function In Streptozotocin-Induced Diabetic Rats, Sarah Elizabeth Neel
Electronic Theses and Dissertations
Background: Streptozotocin (STZ) induced diabetes leads to various complications including cardiomyopathy. Recent data suggests transplanted bone marrow stem cells improve cardiac function in diabetic cardiomyopathy. However, whether modified ES, iPS cells, or factors released from these cells can inhibit apoptosis and fibrosis remains completely unknown. The present study was designed to determine the effects of transplanted ES cells overexpressing pancreatic transcription factor 1 a (Ptf1a), a propancreatic endodermal transcription factor, iPS cells, or their respective conditioned media (CM) on diabetic cardiomyopathy. Methods: Experimental diabetes was induced in male Sprague Dawley rats (8-10 weeks old) by intraperitoneal STZ injections (65 mg/kg …
Role Of Macrophage Apoptosis In Atherosclerosis., June Liu
Role Of Macrophage Apoptosis In Atherosclerosis., June Liu
Electronic Theses and Dissertations
The presence of apoptotic cells in atherosclerotic lesions has been broadly reported in the past ten years. The majority of these apoptotic cells are macrophages. However, the pathogenic role of macrophage apoptosis in the development of atherosclerosis remains to be elucidated. Elevated expression of Bax, one of the pivotal pro-apoptotic proteins of the Bcl-2 family, has been found in human atherosclerotic plaques. Activation of Bax also occurs in free cholesterol-loaded and oxysterol treated mouse macrophages. In this study, we evaluated the influence of Bax deficiency on apoptosis in macrophage-like P388D1 cells by using small interfering RNA (siRNA) to suppress Bax …
Protection Of Pifithrin-Α And Melatonin Against Doxorubicin-Induced Cardiotoxicity., Xuwan Liu
Protection Of Pifithrin-Α And Melatonin Against Doxorubicin-Induced Cardiotoxicity., Xuwan Liu
Electronic Theses and Dissertations
The current studies were designed to explore the protective effects of pifithrin-α and melatonin against doxorubicin-induced cardiotoxicity. Doxorubicin was injected at a dose of 22.5 mg/kg (i.p.) in mice to induce cardiotoxic effects. Meanwhile, doxorubicin caused a significant increase of cardiac cell apoptosis following injection (14.2 ± 1.1% for doxorubicin-5 d vs. 1.8 ± 0.12% for control, P < 0.01). Ribonuclease protection assays and Western blot analyses revealed that doxorubicin upregulated the p53-dependent genes Bax, BclxL, and MDM2 at least 2-fold. p53 was phosphorylated at Ser 15 in mouse hearts 1 h following doxorubicin injection, and p38 and ERK1/2 MAPKs mediated the phosphorylation of p53. In addition, caspases-3 and -9 were activated 24 h after doxorubicin injection. A p53 inhibitor, pifithrin-α, inhibited doxorubicin-induced apoptosis when administered at a dose of 2.2 mg/kg. Pifithrin-α abolished p53 transactivation activity, but did not influence doxorubicin-induced phosphorylation at Ser 15. By effectively inhibiting the expression of p53-dependent genes, pifithrin-α blocked doxorubicin-induced activation of caspases-3 and -9, thereby preventing cardiac apoptosis. In addition, pifithrin-α attenuated doxorubicin-induced structural and functional damages, without diminishing its anti-tumor efficacy on p53-null PC-3 cancer cells. The protective effects of melatonin and its metabolite 6-hydroxymelatonin on doxorubicin-induced cardiac dysfunction were evaluated in an isolated perfused mouse hearts and in vivo doxorubicin-treated mice. While perfusion of mouse hearts with 5 μM doxorubicin for 60 min resulted in a 50% suppression of HRxLVDP and a 50% reduction of coronary flow, pre-exposure of hearts to 1 μM melatonin or 6-hydroxymelatonin eased the cardiac …
The Signaling Pathway Of Oxysterol Induced Apoptosis In Chinese Hamster Ovary (Cho)-K1 Cells., Lin Yang
The Signaling Pathway Of Oxysterol Induced Apoptosis In Chinese Hamster Ovary (Cho)-K1 Cells., Lin Yang
Electronic Theses and Dissertations
Apoptosis, a form of genetically programmed cell death, plays a key role in regulation of cellularity of the arterial wall. During atherogenesis, improper apoptosis may cause abnormalities of arterial morphogenesis, wall structural stability, and metabolisms. It has been well established that vascular cells undergo apoptosis after uptake of oxidized low-density lipoprotein (oxLDL). Thus, an analysis of the signaling pathway of apoptotic induction by oxLDL is of value in understanding the development of atherosclerotic plaque. In order to elucidate the signaling pathway of apoptosis induced by oxLDL, we have used Chinese hamster ovary (CHO)-K1 cells treated with a potent oxysterol, 25-hydroxycholesterol …