Theses and Dissertations from UMD

Permanent URI for this communityhttp://hdl.handle.net/1903/2

New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

Browse

Filters

2007 - 20082

Settings

Subject: search.filters.subject.cell death

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Genetic regulation of autophagic cell death in Drosophila Melanogester
    (2008-11-20) Dutta, Sudeshna; Baehrecke, Eric H; Molecular and Cell Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Apoptosis and autophagic cell death are the two most prominent morphological forms of programmed cell death that occur during animal development. While much is known about the mechanisms that regulate apoptosis, relatively little is known about autophagic cell death. The steroid hormone ecdysone coordinates multiple cellular processes during metamorphosis in Drosophila, including cell differentiation, morphogenesis and death. E93 is necessary and sufficient for larval tissue cell death during metamorphosis, including autophagic cell death of salivary glands. Here we characterize new mutant alleles of a dominant wing vein mutation Vein-off (Vno), and provide evidence that E93 and Vno are related. Our data also indicate that E93 functions in steroid regulation of both cell development and death during metamorphosis. E93 encodes a helix-turn-helix DNA binding motif and binds to specific regions of salivary gland polytene chromosomes. We have used genetic and genomic approaches to identify downstream targets of E93. We have identified numerous candidate E93 target genes using DNA microarrays, and have generated transgenic animals to identify downstream target genes of E93 by chromatin immune precipitation. We show that one putative E93 target gene, hippo (hpo), is required for salivary gland cell death. The Wts/Hpo tumor-suppressor pathway is a critical regulator of tissue growth in animals, but it is not clear how this signaling pathway controls cell growth. Our data indicate that salivary gland degradation requires genes in the Wts/Hpo pathway. Wts is required for cell growth arrest and autophagy in dying salivary glands, and regulates the degradation of this tissue in a PI3K-dependent manner.
  • Thumbnail Image
    Item
    SOURCE DEPENDENT VARIATION IN HYDROXYL RADICAL PRODUCTION BY AIRBORNE PARTICULATE MATTER AND THE IMPACT ON BEAS-2B AND JB6 CELLS
    (2007-04-30) Alaghmand, Marjan; Blough, Neil V; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Numerous studies have shown an association between increased levels of particulate matter (PM) and the exacerbation of lung diseases. The exact means by which PM produces these effects remain unclear. Generation of reactive oxygen species such as the hydroxyl radical (OH), is one of the hypothesized mechanisms. However, the importance OH of production by PM remains uncertain due to a lack of sensitive and selective methods for its determination. In this work, a highly-sensitive fluorescence-based technique was employed to quantify the magnitude of .OH generated by a wide range of airborne particulate matter. The generated .OH was measured in the presence and absence of biological electron donor. Little or no production of .OH was observed in the absence of the added electron donor. For some but not all particles, .OH production was increased substantially when a biological electron donor was present. No detectable .OH was produced by kaolinite or silica. The mechanism(s) of .OH generation by airborne particulate matter were investigated. The presence of dioxygen, hydrogen peroxide, superoxide and metal chelators significantly affected .OH production by the particles. The results indicate that metals and organic constituents are involved in .OH production by particles and occur through both homogeneous and heterogeneous reactions. The effect of different airborne particles on .OH generation in the presence of two different cell lines, lung epithelial cells (BEAS-2b) and mouse epidermal cells (JB6) were investigated. In addition, two different toxicological methods were employed to investigate cell viability in the presence of different airborne particles. Based on our results, some .OH production was observed in the presence of these cell lines when exposed to diesel particulate matter and urban dust, but rates of cell death did not correlate with the .OH production rate. Further, silica particles, which exhibited no evidence of .OH production, produced the most rapid cell death. On the other hand, both cell death and hydroxyl radical formation were dramatically enhanced when an external biological reductant, NADPH, was added to a suspension of cells and urban dust. In this situation, the high flux of .OH is the likely factor causing cell death.