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Characterization Of Altered Epithelial Cell Turnover And Differentiation In Embryonic Murine Lungs That Over-Express Receptors For Advanced Glycation End-Products (Rage), Jeffrey Alan Stogsdill
Characterization Of Altered Epithelial Cell Turnover And Differentiation In Embryonic Murine Lungs That Over-Express Receptors For Advanced Glycation End-Products (Rage), Jeffrey Alan Stogsdill
Theses and Dissertations
Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors highly expressed in the lung that modulate pulmonary inflammation during disease. However, the contributions of RAGE signaling are unknown during pulmonary organogenesis. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, conditional transgenic mice were generated that over-express RAGE in alveolar type II cells of the lung. When RAGE is over-expressed throughout embryogenesis, severe lung hypoplasia ensues, culminating in perinatal lethality. Flow cytometry and immunohistochemistry employing cell-specific markers for various distal cell types demonstrated anomalies in key epithelial cell populations resulting from RAGE up-regulation through …
Defeating Cytoplasmic Sequestration Of P53 In Human Breast Cancer Cells; Is Mortalin Involved?, Sarah Yunes
Defeating Cytoplasmic Sequestration Of P53 In Human Breast Cancer Cells; Is Mortalin Involved?, Sarah Yunes
Honors Theses and Capstones
Cytoplasmic sequestration of p53, possibly caused by p53 interacting with mortalin, can prevent p53 from functioning in DNA repair and apoptosis, causing aberrant growth. This project treated SKBR3 breast cancer cells with MKT-077, a dye that is a competitive binder to mortalin to see if it would result in the release of p53 from the cytoplasm and restoration of p53 function. Treatment resulted in partial translocation of a protein suspected to be p53 to the nucleus and apoptosis initiated at the mitochondria.
Treatment Of Aortic Heart Valve Conduit With Glutamine And Heat Shock As A Means To Deter The Constituent Cellular Population From Becoming Apoptotic, Alyce Marie Linthurst Jones
Treatment Of Aortic Heart Valve Conduit With Glutamine And Heat Shock As A Means To Deter The Constituent Cellular Population From Becoming Apoptotic, Alyce Marie Linthurst Jones
Theses and Dissertations in Biomedical Sciences
Cryopreserved allograft heart valves represent the best solution for a patient with a failing heart valve. However, the constituent cells become apoptotic and within months of transplant the heart valve becomes acellular and the recipient's cells do not repopulate the allograft (3, 51). A strategy to prevent this situation would be to minimize or prevent apoptosis from occurring by strategically altering steps during heart valve processing. Recently it has been demonstrated that: 1) Heat shock protein 70 is a negative modulator of the apoptotic cascade; 2) Cells in culture exposed to hypothermic conditions produce heat shock protein 70 upon rewarming; …
The Role Of Bcl-2 Family In Clinical Response Of Chronic Lymphocytic Leukemia, Sayer Rashed Alharbi
The Role Of Bcl-2 Family In Clinical Response Of Chronic Lymphocytic Leukemia, Sayer Rashed Alharbi
ETD Archive
The anti-apoptotic Bcl-2 proteins regulate lymphocyte survival and are over-expressed in lymphoid malignancies, including chronic lymphocytic leukemia (CLL). The small molecule inhibitor ABT-737 binds with high affinity to Bcl-2, Bcl-xl, and Bcl-w but with low affinity to Mcl-1, Bfl-1, and Bcl-b. The active analog of ABT-737, navitoclax, has shown a high therapeutic index in lymphoid malignancies developing a predictive marker for it would be clinically valuable for patient selection or choice of drug combinations. We compared expression of anti-apoptotic Bcl-2 genes that are known to be targeted by ABT-737. Our findings reveal that the relative ratio of Mcl-1 and Bfl-1 …
Signals Delivered By Interleukin-7 Regulate The Activities Of Bim And Jund In T Lymphocytes, Shannon Moore Ruppert
Signals Delivered By Interleukin-7 Regulate The Activities Of Bim And Jund In T Lymphocytes, Shannon Moore Ruppert
Electronic Theses and Dissertations
Interleukin-7 (IL-7) is an essential cytokine for lymphocyte growth that has the potential for promoting proliferation and survival. While the survival and proliferative functions of IL-7 are well established, the identities of IL-7 signaling components in pathways other than JAK/STAT, that accomplish these tasks remain poorly defined. To this end, we used IL-7 dependent T-cells to examine those components necessary for cell growth and survival. Our studies revealed two novel signal transducers of the IL-7 growth signal: BimL and JunD. IL-7 promoted the activity of JNK (Jun N-terminal Kinase), and that JNK, in turn, drove the expression of JunD, a …
The Dynamic Functions Of Bax Are Dependent On Key Structural And Regulatory Features, Rebecca Boohaker
The Dynamic Functions Of Bax Are Dependent On Key Structural And Regulatory Features, Rebecca Boohaker
Electronic Theses and Dissertations
Bax is an essential mediator of cell fate. Since its discovery in 1985 as a protein that interacts with the anti-apoptotic protein, Bcl-2, key elements related to its function, structure and regulation remains to be determined. To this end, mitochondrial metabolism was examined in non-apoptotic Bax-deficient HCT-116 cells as well as primary hepatocytes from Bax-deficient mice. Although mitochondrial density and mitochondrial DNA content was the same in Bax-containing and Bax -deficient cells, MitoTracker staining patterns differed, suggesting the existence of Bax -dependent functional differences in mitochondrial physiology. Oxygen consumption and cellular ATP levels were reduced in Bax -deficient cells, while …
Nutraceutical Antioxidants And Their Therapeutic Potential In Neurodegeneration, Erika Kristine Ross
Nutraceutical Antioxidants And Their Therapeutic Potential In Neurodegeneration, Erika Kristine Ross
Electronic Theses and Dissertations
Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease that affects motor neurons of the brain and spinal cord. Many studies indicate that mitochondrial oxidative stress (MOS) is a principal mechanism underlying the pathophysiology of this and other devastating neurodegenerative diseases. Here, we investigated a unique whey protein supplement (Immunocal®) to determine its neuroprotective efficacy in several in vitro models of MOS and in an in vivo mouse model of ALS. This non-denatured whey supplement contains cystine which is an oxidized form of cysteine, an essential precursor for synthesis of the endogenous antioxidant, glutathione (GSH). In primary cultured rat cerebellar …
Transplantation Of Pluripotent Stem Cells Confers Cardiac Protection In Dox-Induced Heart Failure Through Notch-1 Pathway, Hilda Merino-Chavez
Transplantation Of Pluripotent Stem Cells Confers Cardiac Protection In Dox-Induced Heart Failure Through Notch-1 Pathway, Hilda Merino-Chavez
Electronic Theses and Dissertations
Doxorubicin (DOX) is the antineoplastic drug of preference used to treat a wide variety of malignancies, with high survival rates among treated patients. However, the benefits of this drug have become less appealing due to the side effects that occur such as DOX-induced cardiomyopathy (DIC) and an increased risk of myocardial infarction (MI). Therefore, there is an urgent need to explore the therapeutic options to treat DIC. In this context, adult stem cells have been used as a source to reduce cardiomyocyte apoptosis in DIC; however, the effects of transplanted embryonic stem (ES) cells and induced pluripotent stem (iPS) cells …
Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin
Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin
Wayne State University Dissertations
Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, compromising p53 activity. Therefore, lymphoma is a suitable model for studying therapeutic value of disrupting HDM2-p53 association by small-molecule inhibitors (SMIs). HDM2 SMIs have been developed and are currently under various stages of preclinical and clinical investigation. This study examined various molecular mechanisms associated and biological effects of two different classes of HDM2 SMIs: the spiro-oxindoles (MI-219) and cis-imidazoline (Nutlin-3) in lymphoma cell lines and patient-derived B-lymphoma cells. Surprisingly, results revealed significant quantitative and qualitative differences between these two agents. At the molecular level, effect of Nutlin-3 was generally more …
Identification Of Epitopes On Ricin Toxin's Enzymatic Subunit (Rta) Critical For Eliciting Neutralizing Antibodies And Protective Immunity, Joanne Marie O'Hara
Identification Of Epitopes On Ricin Toxin's Enzymatic Subunit (Rta) Critical For Eliciting Neutralizing Antibodies And Protective Immunity, Joanne Marie O'Hara
Legacy Theses & Dissertations (2009 - 2024)
Ricin toxin's enzymatic subunit (RTA) is a 267 amino acid RNA N-glycosidase that selectively depurinates eukaryotic ribosomal RNA and arrests protein synthesis. The crystal structure of RTA revealed that the protein assumes three distinct folding domains (FD). Residues within FD1 and FD2 form RTA's active site pocket and are proposed to interface with ribosomal proteins, while FD3's primary function is to associate with ricin's B subunit (RTB). In this study I sought to identify the regions of RTA that are important in eliciting toxin-neutralizing antibodies (TNA), as this information is critical for current efforts to develop RTA-based subunit vaccines. I …
The Role Of Pkr In Transducing The Ribotoxic Stress Response Elicited By Ricin, Lauren Rose-Boehnlein
The Role Of Pkr In Transducing The Ribotoxic Stress Response Elicited By Ricin, Lauren Rose-Boehnlein
Legacy Theses & Dissertations (2009 - 2024)
Ribotoxins such as ricin and T-2 toxin bind to ribosomes and trigger cleavage of 28S rRNA and inhibition of protein synthesis. Upon detection of ribosomal alterations, the cell initiates a ribotoxic stress response (RSR), resulting in activation of the stress-activated protein kinase and mitogen-activated protein kinase (SAPK/MAPK) signaling cascade, upregulated expression of both pro-and anti-apoptotic stress-inducible genes, increased secretion of inflammatory cytokines, and ultimately culminating in apoptosis. While it is not immediately clear the exact mechanism by which ribosomes induce the RSR, nor the exact cellular components involved upstream of MAPK activation, it has recently been proposed, in the case …