Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 16 of 16 for “"SPHK1"”.
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Role and Regulation of Sphingosine 1-Phosphate In Erythrocyte
… the S1P-generating enzyme Sphingosine Kinase 1 (Sphk1) and the absence of S1P degrading enzymes. Erythrocytes are considered only a major reservoir for S1P because they supply S1P to the circulation for the regulation of various physiological processes which include but are not limited to immune …
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Design, Synthesis, and Structure-Activity Relationship Investigation of Selective Sphingosine Kinase Inhibitors
Sphingosine kinase 1 (SphK1) is the key enzyme catalyzing the formation of sphingosine-1-phosphate (S1P), which is an important signaling molecule that regulates multiple biological process including inflammatory responses. Elevated SphK1 activity as well as upregulated S1P levels is linked to …
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Sphingosine Kinase 1 Regulates Fascin Expression to Promote Metastasis In Triple Negative Breast Cancer
… Here, I found that sphingosine kinase 1 (SPHK1) was expressed at higher levels in TNBCs patients samples than in other breast cancer subtypes and high SPHK1 expression is associated with poor survival in TNBC patients. Also, TNBC cell lines have relatively higher expression of SPHK1 at …
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Suppression and activation of lipid signalling in cancer : tumour suppressor PTEN and oncogenic sphingosine kinase
… and cell survival. Sphingosine kinase 1 (SphK1), a known tumour promoter/oncogene, has been shown to activate the PI3K/Akt pathway to enhance resistance to apoptosis. The loss of function of PTEN and/or the overexpression of SphK1 contribute to tumorigenesis. This thesis describes the …
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Design and Synthesis of Orally Bioavailable Sphingosine Kinase 2 Selective Inhibitors
… generative enzyme's sphingosine kinase 1 and 2 (SphK1 and SphK2). Inhibition of SphK1 and SphK2 results in the manipulation of S1P levels, which has been shown to be therapeutic in various animal models of disease. While there are multiple examples of potent SphK1-selective and dual SphK1/2 …
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Regulation of cytokine and chemokine production in macrophages
… regulatory macrophage markers (Arg1, LIGHT and SphK1) was enhanced in MEF2D-deficient cells.<br/>Regulatory macrophages are characterised by high expression of IL-10 amongst other markers. Interestingly, Zymosan stimulation of macrophages leads to a regulatory-like phenotype. Expression of SphK1 …
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Structure-activity relationship studies and biological evaluation of selective sphingosine kinase inhibitors
… 1.2 µM) and SLP7111228 (>200 fold selective for SphK1 with a Ki of 48 nM). In vitro studies in U937 cells yielded a decrease in S1P levels with the introduction of inhibitors. Mouse studies provided insight into the pharmacokinetic effect of our SphK2-selective inhibitors, revealing an increase …
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Structure-Activity Relationship Studies of Sphingosine Kinase Inhibitors and Mitochondrial Uncouplers
… kinase (SphK) and SphK exists as two isoforms-"SphK1 and SphK2, which differ with respect to their cellular activity and localization. As the key mediators in the synthesis of S1P, SphKs have attracted attention as viable targets for pharmaceutical inhibition. To validate their potential as …
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Design, synthesis, and biological evaluation of selective sphingosine kinase inhibitors
… SphK exists as two different isoforms, namely SphK1 and SphK2, which play different roles inside the cell. The dearth of isoenzyme-selective inhibitors has been a stumbling block for probing the exact roles of these two isoforms in disease progression. This report documents our efforts in …
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Structure Activity Relationship Studies on Isoform Selective Sphingosine Kinase Inhibitors
… by the two isoforms of sphingosine kinase (SphK1 and SphK2). Therefore, SphKs are a potential therapeutic target; however, the physiological role of SphK2 is still emerging. In order to determine the role of SphK2 in vivo, more potent and selective small molecule inhibitors of SphK2, as well …
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Biological Clocks, Inflammation, and Multiorgan Damage In Sickle Cell Disease
… confirmed that elevated sphingosine kinase 1 (SphK1) mediates sphingosine-1-phosphate (S1P) production to promote erythrocyte sickling. S1P signals via five S1P receptors (S1PR) regulates several pathophysiological functions.</p> <p>In the first chapter of this dissertation, I explored the role …
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Functional Investigation of Genetic Determinants of Red Blood Cell Traits
… (PIEZO1, TMC8 ), sphingolipid signalling (PLD1, SPHK1, S1PR2), iron homeostasis (TF, TFR2) and nucleotide metabolism (GMPR, PKLR). To uncover the function of candidate genes in relation to red blood cell development, I established protocols to generate CRISPR/Cas9-based model systems in human …
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Establishment and characterisation of chemoresistant osteosarcoma cell lines by single and multi-agent induced strategies
… to epithelial gene signalling occurred.SPHK1 and HIF1A were upregulated in most of the resistant models from the PCR array analysis and SPHK1 protein level was also determined to increase in MG-63/CISR8 (2.03 ± 0.08-fold, p=0.034), MG-63/DOXR8 (1.77 ± 0.24-fold, p=0.02), and …
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Rol de los esfingolípidos en los procesos activados por estrés oxidativo en neuronas y células gliales de retina
… de las cuales se conocen dos isoformas, SphK1 y SphK2. Con diversas técnicas citoquímicas, determinamos que DHA protege a los fotorreceptores de la apoptosis por daño oxidativo o por agregado de ceramida o esfingosina, y que la inhibición de la formación de S1P, catalizada por la SphK1 …
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IGF2R: A NEW PLAYER IN THE INSULIN LIKE GROWTHFACTOR 2 (IGF2) PATHWAY SUSTAINING ADRENOCORTICAL TUMOURS CELL GROWTH
… the overexpression of SphK, mainly the isoform SphK1, in ACT compared to NA. Moreover, this was the first project to correlate IGF2R with SphK in ACT, proving that in case of IGF2R knockdown or inhibition the activity of SphK is hampered. The identification of these novel actors in the ACT …
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"Rol de los lípidos en la regulación de la diferenciación, proliferación y supervivencia de neuronas de retina"
… La inhibición de la esfingosina quinasa 1 (SphK1), enzima involucrada en la síntesis de S1P, con un inhibidor competitivo, el DHS, bloqueó los efectos del GDNF y del DHA sobre la proliferación y diferenciación de las neuronas fotorreceptoras. Evaluamos entonces a través de qué mecanismos el …