碩士 / 國立臺灣海洋大學 / 生命科學暨生物科技學系 / 103 / Hypoxia inducible factors are the major regulators involved in hypoxia adaptation. In normoxic environment, hypoxia-inducible factors 1α and -2α are hydroxylated and ubiquitinated and subsequently degraded by proteosomes. Under hypoxic stress, these factors are stabilized and enter nucleus to activate a number of genes involved in angiogenesis, erythropoiesis, and anaerobic metabolism. The aerobic metabolism is also repressed by pyruvate dehydrogenase kinase (PDK) under hypoxic environment. Recent studies demonstrated that the proliferating stem cells and malignant cells display high level of anaerobic or aerobic glycolysis. Since HIF1α and -2α have critical roles in erythropoiesis and CNS development, respectively, it suggests these factors are presented in active form in neural and erythroid progenitor cells. By using tirapazamine which preferentially attacked the hypoxic cells, here I detected specific hypoxic signaling in the developing CNS neural cells and ICM erythroid progenitor cells at 24 hpf stages of zebrafish embryos. It may explain how HIFα proteins are kept in active form in neural and ICM cells. As analyzed by Hypoxyprobe-1 staining, there was no significant hypoxia signal detected in normal developing embryos. Nevertheless, continuous exposure to 2% oxygen concentration induced significant hypoxia signaling over the entire embryo, specifically in brain and vertebrate neurons. Apparently the Hypoxyprobe-1 is less sensitive to detect intracellular hypoxia stress than tirapazamine assay, but it responds to hypoxic extracellular microenvireonment more sensitive than tirapazamine. To investigate whether the local hypoxia microenvironment in the developing embryos induces anaerio metabolism, I have studied the expression patterns of various glycolytic genes in the developing embryos. It appears that most of glycolytic genes expressed in CNS regions. It consists with the results of hypoxia signaling in the developing embryos.
| Identifer | oai:union.ndltd.org:TW/103NTOU5613005 |
| Date | January 2015 |
| Creators | Chen, Yi-Rong, 陳意容 |
| Contributors | Hu, Chin-Hwa, 胡清華 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 40 |
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