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Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Pharmaceutical Science." Includes bibliographical references (p. 138-153).

Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Nutritional Sciences." Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 183-216). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 57-63). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 57-63). Also available on the Internet.

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Incompatible plant/pathogen interactions are often manifested as the hypersensitive response (HR), characterised by host cell death and rapid tissue collapse at the site of attempted infection. A key early response during the HR is the generation of reactive oxygen species (ROS), such as the superoxide anion ( 0; -) and hydrogen peroxide (H20 2), in an oxidative burst. The ROS produced during the oxidative burst have been implicated as cellular signalling molecules for the induction of defences responses including hypersensitive cell death. Increasing evidence exist that the free radical, nitric oxide (NO) also acts as a signalling molecule in plants during plant/pathogen interactions. The generation of NO in response to bacterial challenge, and the potential signalling pathways involved in H20 2- and NO-induced defence responses in Arabidopsis were therefore investigated Arabidopsis suspension cultures were found to generate elevated levels of NO and undergo cell death analogous to HR seen in planta, in response to challenge by avirulent bacteria. Using NO donors, elevated levels of NO were found to be sufficient to induce cell death independently of ROS, but not the expression of the defence-related genes PAL or GST. The NO-induced cell death was sensitive to inhibitors of RNA processing and protein synthesis, suggesting that NO-induced cell death is a form of programmed cell death (PCD), requiring the expression of at least one gene. However, the source of NO production by Arabidopsis remains to be elucidated, but appears to be independent of nitric oxide synthase-like activity. Pharmacological studies using specific inhibitors of mammalian mitogen activated protein kinase (MAPK) signalling cascades, and guanylate cyclase, the enzyme responsible for the production of second messenger cyclic guanosine monophosphate (cGMP), suggest that a MAPK signalling cascade acts downstream or independently of the oxidative burst to initiate H20 2-induced defence responses, while NO-induced cell death requires the production of cGMP in Arabidopsis. A number of studies have attempted to establish whether PCD induced during the HR in plants is similar to apoptotic cell death of anin1al cells. The key executioners of apoptosis in animal cells are caspases. NO was found to induce caspase-like activity in Arabidopsis cells, while a specific inhibitor of caspase-l blocked harpin-, H20 2- and NO-induced cell death. A characteristic of apoptosis is chromatin condensation and DNA fragmentation into nucleosomal fragments. Chromatin condensation was observed in Arabidopsis cells treated with the NO donor Roussin's black salt, but no DNA fragmentation was found in DNA extracted from cells treated with harpin, H20 2 or NO. In addition, random DNA degradation indicative of necrosis was found in DNA extracted from cells following avirulent bacterial challenge.

Optic nerve section (ONS) is an experimental model for damage of the optic nerve associated with diseases such as glaucoma and optic neuritis. Damage to the optic nerve causes loss of retinal ganglion cells that are attached, once the cells are damaged, they are not typically replaced. Recently, Fischer and Reh (2003) found that Müller glia have the potential to adopt phenotypes and functional capabilities similar to those of retinal progenitors, a potential source of retinal regeneration. In the chick, when the specific retinal cells are targeted for damage by chemotoxins, there is widespread apoptosis but also mitotically active cells that label with retinal progenitor markers. Fischer and Reh (2002) also discovered that the combination of growth factors FGF2 and insulin is capable of stimulating the regenerative response of the Müller glia to retinal progenitor cells in chick eyes. This study was conducted to analyse damage to the ganglion cells by optic nerve section in chicks to determine the effect of age on the cell death timeline, the proliferative qualities of the retina and to see if injections of growth factors had the ability to increase the proliferation. Histological methods were used to analyse cellular changes and ultrasound to monitor eye growth. Apoptotic activity preceded retinal thinning and ganglion cell loss, indicating that ONS-related cell death is mediated at least in part by apoptotic mechanisms and age did not affect the time course, although, age did affect the eye growth changes, which may be attributed to the plasticity of the younger eyes. ONS damage elicited proliferative activity in the retina as did growth factor injections alone. The combination of ONS damage and growth factor injections increased the proliferative activity and the overall total number of cells in the ganglion cell layer. These findings can potentially lead to the development of therapeutic strategies for the preservation or restoration of retinal cells in diseased eyes.

Programmed cell death (PCD) is pervasive in eukaryotes, playing a fundamental role in development. PCD in animals has been studied in detail, partly due to Caenorhabditis elegans, a worm whose anatomy allowed for the investigation of exactly 131 cells that die via PCD. Elucidating this complex pathway in this simple worm laid the foundation for further insights into mammalian PCD. Overall, less is known regarding PCD in plants, where cell death is broadly separated into developmentally regulated and environmentally induced. The lace plant (Aponogeton madagascariensis) undergoes developmentally regulated PCD to form perforations between longitudinal and transverse veins over its leaf surface. The optimization of protoplast isolation and induced cell death via heat shock (HS) in the lace plant is detailed here. Following HS, protoplasts displayed characteristics of PCD including: Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive nuclei, increases in vesicles as well as Brownian motion, and plasma membrane blebbing. Additionally, mitochondrial dynamics were investigated, and a role for the mitochondrial permeability transition pore (MPTP) was indirectly established via cyclosporine A (CsA) experimentation. The main focus of this dissertation was to elucidate cellular dynamics during developmentally regulated PCD in the lace plant, which is visibly discernable during the window stage of leaf development. A single areole within a window stage leaf was further divided into three areas based on the progression of PCD; non-PCD (NPCD) cells, early PCD (EPCD) cells, and late PCD (LPCD) cells. Using this gradient, mitochondria were delineated into four stages based on distribution, motility, and membrane potential. Additionally, it was determined that the MPTP also played a role in developmental lace plant PCD, as inhibition of the pore with CsA not only reduced caspase-like proteases (CLPs) but also stopped perforation formation. Furthermore, the actin cytoskeleton was also investigated, with evidence suggesting it as a possible target for CLPs. The novel use of lace plant leaves for long-term live cell imaging allowed for the establishment of a timeline of cellular events that occur during developmental PCD. Major conclusions of this dissertation reveal various similarities between environmental induced and developmentally regulated PCD in this one plant species.