Thesis (Ph. D.)--University of Oregon, 2002. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 102-119). Also available for download via the World Wide Web; free to University of Oregon users.

Oxygen is known to sensitize X-irradiated cells to lethal radiation damage. At low ambient oxygen tensions, however, the molecular mechanisms of the sensitization process and the metabolic requirements of the cell may be forced to compete for the cellular oxygen supply. The effect of cell respiration on the availability of intracellular oxygen during irradiation was consequently investigated by comparing the radiosensitivities of respiring and non-respiring cells. Cultured mammalian cells were irradiated in single cell suspensions and thin film monolayers at respiration inhibiting (4°C) and at normal cell culturing (37°C) temperatures. Due to oxygen equilibration and radiolytic depletion problems, the results of the suspension culture experiments were inconclusive. By subsequently analyzing the diffusive mass transfer of oxygen in the suspension medium, the stirrer flask was determined to be an inappropriate culture vessel in which to irradiate cells at constant low oxygen concentrations. A thin film cell culture system in which the oxygen concentrations to which the cells were exposed during irradiation could be more accurately controlled was then developed. A comparison of the oxygen enhanced radiosensitivities of the respiring and non-respiring cells in thin film monolayers suggested that the metabolic depletion of oxygen at low oxygen tensions has a significant effect on the local and intracellular oxygen distribution. These effects are representative of those that would be produced if respiration induced oxygen gradients existed inside and immediately around respiring cells. The magnitude of the differential radiosensitivities was found to be dependent on cell shape and to have values that agreed very well with theoretical predictions based on the existence of such gradients. / Science, Faculty of / Physics and Astronomy, Department of / Graduate

Graduation date: 1995

Thesis (M.Sc.) --University of Adelaide, 1946. / Typewritten copy.

M.Tech. / Low-intensity laser irradiation (LILI), also known as photo-biostimulation, is a type of phototherapy which is based on the application of low power monochromatic and coherent light mostly in the wavelength range of 600 to 1 000 nm to injuries and lesions to stimulate healing. LILI has been shown to increase adenosine triphosphate (ATP) synthesis, cell proliferation (Silveira et al., 2007 and 2009; Hawkins and Abrahamse, 2006a) and collagen synthesis, and release of growth factors from cells (Eells et al., 2004). LILI has not been fully embraced and is mainly due to the fact that the biochemical mechanisms underlying the positive effects are not completely understood (Hamblin and Demidova, 2006). Though the mechanisms of photo-biostimulation on a variety of mitochondrial enzymes have been proposed and studied by different researchers, most of the mechanisms are based on oxygen consumption studies and lack direct experimental support (Chen et al., 2008). This project was designed to study the enzyme activity and expression of the mitochondrial respiratory chain complexes (I to V) post-irradiation with a wavelength of 660 nm and a fluence of 5 or 15 J/cm2 in isolated human skin fibroblast cells. Diabetes mellitus (DM) is a group of diseases marked by high levels of blood glucose resulting from defects in insulin production, insulin action or both. It is found worldwide and is estimated to affect 1.1% of the world population (World Health Organization, WHO, 2002). Estimates from 2009 by the International Diabetes Federation suggest that the number of adults with diabetes in the world will expand by 54%, from 284.6 million in 2010 to 438.4 million in 2030. The projected growth for sub-Saharan Africa is 98%, from 12.1 million in 2010 to 23.9 million in 2030 (Mbanya et al., 2010). Though DM is more common in industrialized countries, the trend is changing.

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Includes bibliographical references (p. 161-180).

No description available.

Bone has several crucial functions including mechanical support of movement, hematopoiesis, maintenance of mineral homeostasis, and energy regulation. Bone also undergoes continuous remodeling to maintain its structural integrity, which suggests it has strong respiration and energy consumption capability. It has been shown that during development, bones, in particular, osteoblasts, rely on glucose uptake for proper skeletal development. However, the effect of energy utilization on osteocytes’ function is currently unknown. Osteocytes are terminally differentiated osteoblasts and are deeply embedded into the mineralized matrix of bone. Previous studies have shown that PTH promotes bone anabolism, in part, by stimulating osteoblasts anaerobic glycolysis while suppressing glucose oxidation through the TCA cycle. In osteocytes, PTH suppresses Sost expression (the gene encoding a potent inhibitor of bone formation) by inducing HDAC4/5 nuclear translocation and MEF2C inhibition. Recently, Scriptaid, an HDAC complex inhibitor, has been shown to induce Mef2 expression and exercise-like adaptation in mouse muscles. In myocytes, Scriptaid disrupts the HDACs co-repressor complex and induces nuclear export of HDAC4/5 with MEF2 activation. This will subsequently increase the expressions of several genes related to energy utilization such as Glut4 and Pdk4. Thus we hypothesized that Scriptaid might regulate Sost and Glut4 expression in osteocytes. To investigate the effect of Scriptaid on osteocytes, we treated a mouse osteocytic cell line, Ocy454-12H, with Scriptaid. Unexpectedly, Scriptaid potently suppressed Sost, whereas it increased Glut4 expression. Scriptaid stimulated osteocyte respiration and glucose consumption rate. Mechanistically, Scriptaid treatment of Ocy454-12H induced nuclear translocation of Hdac5 whereas it did not affect Hdac4. Silencing of Hdac5 expression with shRNA increased Sost basal expression and blocked Sost suppression induced by Scriptaid. However, Glut4 up-regulation by Scriptaid was independent of the HDAC4/5-MEF2C pathway. Glut4 luciferase reporter assays demonstrated that two additional transcription factors binding sites, O/E&NF1 and C/EBPα, may mediate Scriptaid-induced Glut4 up-regulation. Taken together, these data demonstrate that in osteocytes Scriptaid suppresses Sost expression through regulating HDAC5-MEF2C signaling. However, Scriptaid increases Glut4 expression through Hdac5-independent mechanisms, and dependent on O/E&NF1 and C/EBPα.

The energy supplies of modern society seem to be necessarily associated with risks. In this paper, we address the question as to whether the efficient utilisation of energy in biological systems is also coupled to hazards. Most organisms oxidise highly reduced substrates with molecular oxygen in order to gain energy. In eukaryotes, this process takes place at the inner membrane of specialised organelles, the mitochondria. Interestingly, about 1% of the consumed oxygen molecules are reduced not to water, but to ROS (reactive oxygen species), which are deleterious to many macromolecules, including mitochondrial DNA. As a result, mitochondrial DNA mutations accumulate, in turn affecting the energy supply and inducing degeneration and ageing. / Nach dem heutigen Stand der Technik scheint eine ausreichende Energieversorgung der Gesellschaft stets mit Risiken verbunden zu sein. Wir gehen in dem Artikel der Frage nach, ob auch biologische Systeme bei der Nutzung von Energie Risiken in Kauf nehmen. Zur effizienten Energiegewinnung nutzen Organismen meist Sauerstoff zur Oxidation energiereicher Substrate. In Eukaryonten erfolgt die Energiegewinnung vor allem an der inneren Membran von Mitochondrien. Etwa 1 % des verbrauchten Sauerstoffs wird dabei nicht zu Wasser, sondern zu ROS (reactive oxygen species, reaktive Sauerstoffspezies) reduziert, die unter anderem die mitochondriale DNA schädigen und Mutationen hervorrufen. Diese akkumulieren auf Dauer und führen zu einer Störung der Energiegewinnung, in deren Folge Degenerations- und Alterungsphänomene auftreten.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 128-141).