81 |
CARDIAC POTASSIUM CHANNEL HERG IS REGULATED BY UBIQUITIN LIGASE NEDD4-2SHALLOW, HEIDI 15 August 2011 (has links)
The cardiac rapidly activating delayed rectifier potassium channel (IKr) is encoded by the human ether-a-go-go related gene (hERG), which is important for repolarization of the cardiac action potential. Reduction in hERG expression levels due to genetic mutations or drugs causes Long QT Syndrome (LQTS). Recently, we demonstrated that ubiquitination of hERG channels is involved in low K+ induced hERG endocytic degradation. Since homeostatic degradation is an important pathway in maintaining hERG membrane expression levels, we investigated the molecular mechanisms for hERG degradation by focusing on the role and consequence of overexpressing the ubiquitin (Ub) ligase, Nedd4-2 (Neural Precursor Cell- Expressed Developmentally Downregulated Gene 4- 2) (Yang & Kumar, 2010). Previous work in the lab demonstrated that Ub plays a role in the internalization of cell-surface hERG channels, and I hypothesized that ubiquitination of hERG channels is facilitated through Nedd4-2. To study the effects of Nedd4-2 on hERG channels, I overexpressed Nedd4-2 in human embryonic kidney (HEK) 293 cells that stably express the hERG channels. Electrophysiological recordings, Western blot, co-immunoprecipitation analysis, and confocal microscopy were performed to identify Nedd4-2’s role in hERG expression. The data from whole-cell patch clamp recordings demonstrated that, among hEAG, Kv1.5 and hERG, Nedd4-2 specifically eliminates the hERG channel current. Western blot and confocal imaging analyses showed that Nedd4-2 overexpression led to a significant reduction in mature hERG channels in the plasma membrane. Data obtained using co-immunoprecipitation indicated that Nedd4-2 significantly increases ubiquitinated hERG channels. These data indicate that Nedd4-2 may play a role in hERG homeostatic degradation. / Thesis (Master, Physiology) -- Queen's University, 2011-08-15 18:17:00.452
|
82 |
恋人と結婚相手に対して求めるものの違い - 性差と恋人の捉え方・恋愛経験の有無から -天谷, 祐子, AMAYA, Yuko 27 December 2005 (has links)
国立情報学研究所で電子化したコンテンツを使用している。
|
83 |
Isothiocyanate induction of apoptosis in cells overexpressing Bcl-2Brown, Kristin Kate January 2006 (has links)
The oncogenic protein Bcl-2 is overexpressed in many cancers and prevents cells from undergoing apoptosis in response to traditional chemotherapeutic agents. Recent research has focussed on the development of novel agents that can disrupt the function of Bcl-2 and trigger apoptosis in cancer cells. The isothiocyanates are a class of naturally-occurring phytochemical with potential for development as both chemopreventive and chemotherapeutic agents. This thesis investigated the ability of the isothiocyanates to induce apoptosis in cells that overexpressed Bcl-2. Initially, phenethyl isothiocyanate was shown to be cytotoxic to the Jurkat Tlymphoma cell line with an LD50 of 7.4 µM. Bcl-2 expression had little protective effect, and even greater than 50-fold overexpression only increased the LD50 to 15.1 µM. Morphological and biochemical assays indicated that death still occurred by apoptosis despite overexpression of Bcl-2. A variety of other isothiocyanates were also screened for cytotoxic activity. While the isothiocyanate moiety was crucial for induction of apoptosis, the chemistry of the side chain attached to the isothiocyanate moiety also profoundly influenced the ability of an isothiocyanate to kill Bcl-2 overexpressing cells. The aromatic isothiocyanates were generally far more cytotoxic than aliphatic isothiocyanates. However, within the aromatic isothiocyanates tested in this study the length of the carbon linker group, between the phenyl ring and the isothiocyanate moiety, also influenced cytotoxic activity. Phenethyl isothiocyanate was identified as the most promising compound when targeting cells that overexpressed Bcl-2. Given that minor structural alterations significantly altered cytotoxic activity it is hypothesised that specific interactions with cellular targets may mediate induction of apoptosis by the isothiocyanates. Finally, using a sensitive proteomic technique to label oxidised thiol proteins a preliminary investigation of the targets of the isothiocyanates was performed. A number of thiol proteins were selectively modified following exposure to phenethyl isothiocyanate. One thiol protein that consistently changed was identified as mitochondrial peroxiredoxin-3. Changes to the oxidation state of peroxiredoxin-3 occurred well before activation of apoptosis and may play a role in mediating induction of apoptosis in cells that overexpress Bcl-2. The results of this thesis have provided a platform to permit further investigation of the chemotherapeutic potential of the isothiocyanates and investigation of the mechanisms that allow the isothiocyanates to induce apoptosis in cells that overexpress the oncogene Bcl-2. In the future, the identification of primary targets of the isothiocyanates may aid the design and testing of novel anticancer drugs, and it will also provide novel insight into the regulation of apoptosis.
|
84 |
Molekulare Charakterisierung des Interleukin-2-Gens von Schaf-, Ziegen- und Rinderarten sowie Kartierung und funktionelle Analyse von DNA-Varianten des Interleukin-2-Gens von Ovis aries /Lühken, Gesine. January 2007 (has links)
Universiẗat, Diss., 2007--Giessen.
|
85 |
Disturbed islet function and alterations in islet protein expression /Ortsäter, Henrik, January 2005 (has links)
Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 5 uppsatser.
|
86 |
Analysis of genetic alterations in patients affected with neurofibromatosis Type 2 and its associated tumors /Hansson, Caisa Marie, January 2006 (has links)
Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.
|
87 |
Music and ideasAnna S. Thorvaldsdottir. Anna S. Thorvaldsdottir. Anna S. Thorvaldsdottir. Anna S. Thorvaldsdottir. January 2008 (has links)
Thesis (M.A.)--University of California, San Diego, 2008. / Accompanying disc contains sound files of recordings of the musical compositions. The 1st work for 13 instruments; 2nd for 2 oboes, 2 clarinets, 2 bassoons, and 2 horns; 3rd for voice, 6 stethoscopes, and computer which manipulates sounds picked up by the stethoscopes. Title from first page of PDF file (viewed July 11, 2008). Available via ProQuest Digital Dissertations. Includes bibliographical references: P. 137.
|
88 |
Chemokines and chemokine receptors that mediate immune defense to genital herpes simplex virus type 2 (HSV-2) infectionThapa, Manoj, January 2008 (has links) (PDF)
Thesis (Ph. D.)--University of Oklahoma. / Vita. Bibliography: leaves 141-165.
|
89 |
Études des mécanismes effecteurs et modulateurs impliqués dans les effets cardio-vasculaires des endothélines-1 et 2 ainsi que leurs précurseurs chez le lapinGratton, Jean-Philippe. January 1998 (has links)
Thèses (Ph.D.)--Université de Sherbrooke (Canada), 1998. / Titre de l'écran-titre (visionné le 20 juin 2006). Publié aussi en version papier.
|
90 |
Analyse de l'expression des homologues Bcl-2 au cours du développement de l'intestin humainCardin, Éric. January 2002 (has links)
Thèses (M.Sc.)--Université de Sherbrooke (Canada), 2002. / Titre de l'écran-titre (visionné le 17 juillet 2006). Publié aussi en version papier.
|
Page generated in 0.0276 seconds