• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 3
  • 2
  • Tagged with
  • 5
  • 5
  • 5
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Studies on signals mediating or preventing the intracrine induction of chromatin compaction and cell death by high molecular weight fibroblast growth factor 2

Ma, Xin 05 April 2011 (has links)
Fibroblast growth factor 2 (FGF2) is a multifunctional protein translated as CUG-initiated, high molecular weight (hi FGF2) or AUG-initiated, low molecular weight (lo FGF2) isoforms with potentially distinct functions. Previous work showed that overexpression of hi- but not lo FGF2 elicited chromatin compaction resulting in cell death, by an intracrine route. A series of studies were undertaken aimed at extending our understanding of the intracrine action of Hi FGF2. Major findings are as follows: a. Hi FGF2 overexpression induces apoptotic cell death, as indicated by increased TUNEL staining, and mitochondrial participation (cytochrome c release to cytosol, rescue of the hi FGF2 phenotype by the anti-apoptotic protein Bcl-2. b. Increased expression of pro-survival signals/proteins that are known to upregulate Bcl-2, such as nuclear Akt; the PIM-1 kinase; and the heat shock protein hsp70, also rescued the hi FGF2-induced phenotype. c. The hi-FGF2 effect was associated with sustained, intracrine, activation of ERK, and was blocked by ERK inhibitors. d. FGF2 isoform specific affinity chromatography followed by mass spectroscopy identified several proteins as potentially interacting with hi FGF2; of these, the p68 RNA helicase and the hsp70 were further confirmed as interacting partners, by co-immunoprecipitation. e. Increased nuclear co-localization, and possibly interaction, between hi FGF2 and overexpressed hsp70 correlated with rescue from hi FGF2 induced cell death. f. Factors associated with cardiac pathology (isoproterenol, angiotensin II, endothelin I) also upregulated endogenous hi FGF2 in cardiac cells in culture. Adriamycin-induced cardiotoxicity in the rat, known to be linked to increased incidence of apoptosis, was also associated with increased endogenous hi FGF2. g. Hi FGF2 is expressed in the human heart (atria) and localizes in both cytosol and nuclei, suggesting a participation in human heart physiology and pathophysiology. Work presented here is consistent with the notion that endogenous hi FGF2 up-regulation may play a role in promoting cell death during prolonged tissue stress and dysfunction. It follows that processes related to hi FGF2 upregulation, hi FGF2-nuclear protein interactions and mechanisms of hi FGF2 induced cell death, represent potential therapeutic targets for modulating cell death.
2

Studies on signals mediating or preventing the intracrine induction of chromatin compaction and cell death by high molecular weight fibroblast growth factor 2

Ma, Xin 05 April 2011 (has links)
Fibroblast growth factor 2 (FGF2) is a multifunctional protein translated as CUG-initiated, high molecular weight (hi FGF2) or AUG-initiated, low molecular weight (lo FGF2) isoforms with potentially distinct functions. Previous work showed that overexpression of hi- but not lo FGF2 elicited chromatin compaction resulting in cell death, by an intracrine route. A series of studies were undertaken aimed at extending our understanding of the intracrine action of Hi FGF2. Major findings are as follows: a. Hi FGF2 overexpression induces apoptotic cell death, as indicated by increased TUNEL staining, and mitochondrial participation (cytochrome c release to cytosol, rescue of the hi FGF2 phenotype by the anti-apoptotic protein Bcl-2. b. Increased expression of pro-survival signals/proteins that are known to upregulate Bcl-2, such as nuclear Akt; the PIM-1 kinase; and the heat shock protein hsp70, also rescued the hi FGF2-induced phenotype. c. The hi-FGF2 effect was associated with sustained, intracrine, activation of ERK, and was blocked by ERK inhibitors. d. FGF2 isoform specific affinity chromatography followed by mass spectroscopy identified several proteins as potentially interacting with hi FGF2; of these, the p68 RNA helicase and the hsp70 were further confirmed as interacting partners, by co-immunoprecipitation. e. Increased nuclear co-localization, and possibly interaction, between hi FGF2 and overexpressed hsp70 correlated with rescue from hi FGF2 induced cell death. f. Factors associated with cardiac pathology (isoproterenol, angiotensin II, endothelin I) also upregulated endogenous hi FGF2 in cardiac cells in culture. Adriamycin-induced cardiotoxicity in the rat, known to be linked to increased incidence of apoptosis, was also associated with increased endogenous hi FGF2. g. Hi FGF2 is expressed in the human heart (atria) and localizes in both cytosol and nuclei, suggesting a participation in human heart physiology and pathophysiology. Work presented here is consistent with the notion that endogenous hi FGF2 up-regulation may play a role in promoting cell death during prolonged tissue stress and dysfunction. It follows that processes related to hi FGF2 upregulation, hi FGF2-nuclear protein interactions and mechanisms of hi FGF2 induced cell death, represent potential therapeutic targets for modulating cell death.
3

Investigation of non-autonomous control of cell death and corpse clearance in the ovary of Drosophila melanogaster

Mondragon, Albert Aaron 27 February 2019 (has links)
Cell death is a fundamental aspect of development and homeostasis; its dysregulation is commonly associated with disease. Historically, apoptosis has been the most heavily studied type of cell death, but there are many other non-apoptotic forms of cell death. The Drosophila ovary provides a powerful in vivo model to study non-apoptotic cell death. Each egg chamber in the ovary contains 15 nurse cells that support an oocyte throughout development, and at the end of oogenesis the nurse cells are surrounded by stretch follicle cells and undergo non-apoptotic cell death. The work in this dissertation investigated the role of stretch follicle cells in nurse cell death. Genetic ablation of the stretch follicle cells revealed that they are required for multiple nurse cell death events including the transport of cytoplasm to the oocyte and DNA fragmentation. We found that phagocytic machinery is required in the stretch follicle cells for the acidification and elimination of nurse cells, suggesting nurse cells die by phagoptosis. Furthermore, live imaging and a transgenic engulfment detector demonstrated that nurse cells are not engulfed piece-wise despite the requirement of phagocytosis machinery, but are instead surrounded and acidified extracellularly. To determine the mechanism driving nurse cell acidification, we performed a targeted RNAi screen against lysosome-associated genes. Using tissue-specific RNAi, we demonstrated that the V-ATPase proton pump is required in the stretch follicle cells for nurse cell acidification. GFP fusion proteins and antibody staining revealed that V-ATPases become enriched and localize to the stretch follicle cell plasma membranes to acidify the nurse cells that they surround. Following acidification, the stretch follicle cells were found to release cathepsins, lysosomal proteases, to break down and degrade the nurse cell. To uncover novel pro-death proteins that mediate signaling between the stretch follicle cells and nurse cells, we utilized proximity-dependent protein labeling and identified proteins enriched in the stretch follicle cells. Altogether this work uncovers a new role for lysosomal machinery acting at the plasma membrane of stretch follicle cells to drive nurse cell death, and identifies pro-death proteins in the stretch follicle cells that promote nurse cell death.
4

Discovery of Non-Apoptotic Cell Death Inducers for Triple Negative Breast Cancer (TNBC) Therapy

Malla, Saloni 15 June 2023 (has links)
No description available.
5

Synthesis and Evaluation of Inducers of Methuotic Cell Death and Preliminary Identification of Their Cellular Targets in Glioblastoma Cells

Robinson, Michael W. 21 August 2013 (has links)
No description available.

Page generated in 0.0803 seconds