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The early effects of phorbol esters in the lymphocyte membraneKwong, Cheung Hing. January 1982 (has links)
Thesis (Ph. D.)--University of Wisconsin--Madison, 1982. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.
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Oxonium Ylide Rearrangements: A Novel Approach Towards the Synthesis of the Phorbol SkeletonStewart, Craig 06 1900 (has links)
Oxonium ylides are highly reactive intermediates that can be used for the synthesis of heterocyclic and carbocyclic frameworks. These putative intermediates are almost exclusively formed from diazocarbonyl derived metallocarbenes, by attack of a pendent oxygen atom. Oxonium ylides have been shown to furnish products derived from the [1,2]-shift (Stevens rearrangement) or the [2,3]-shift in an efficient manner. Chapter 1 is a review of oxonium ylides in synthesis focusing on factors that influence the reactivity of these intermediates.
Previous work has shown that the sulfur-directed Stevens rearrangement is an efficient reaction for the generation of seven and eight-membered oxa-bridged carbocycles fused to five-membered rings. Chapter 2 describes an extension of this chemistry where six-seven and six-eight membered oxa-bridged carbocyclic products were furnished in good yields. The chemo- and diastereoselectivity of these rearrangements was dependent on the configuration of the acetal stereocentre present in the diazoketone precursor.
A novel approach towards the synthesis of the tigliane and daphnane diterpenes is described in Chapter 3. The tricyclic framework was generated from a highly stereoselective oxygen-directed Stevens rearrangement of an oxonium ylide. This methodology provides a straightforward route to the construction of the five-seven-six ring system found in these classes of natural products.
Finally, the sulfur-directed Stevens [1,2]-shift was employed in an attempted total synthesis of the natural product (+)-phorbol in Chapter 4. Several variations of the original synthetic scheme were examined, in an effort to construct the core 6-7 ring structure. The Stevens rearrangement was found to provide the 6-7 ring system of phorbol in excellent yield. The chemo- and diastereoselectivity of this rearrangement was dependent on the configuration of the acetal centre as well as the conformation of the six-membered ring in the starting material. In the future, this advanced intermediate could be used to achieve the total synthesis of (+)-phorbol.
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Oxonium Ylide Rearrangements: A Novel Approach Towards the Synthesis of the Phorbol SkeletonStewart, Craig Unknown Date
No description available.
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Role of protein kinase C isoforms in the agonist-stimulated activity of phospholipase D in gliaMallon, Barbara S. January 1996 (has links)
No description available.
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Sources of Diradylglycerols Generated During Cell Growth and Phorbol Ester Stimulation in Madin-Darby Canine Kidney CellsRobinson, Mitchell, Warne, Thomas R. 02 August 1991 (has links)
The molecular species of diacylglycerol and alkylacylglycerol of Madin-Darby canine Kidney (MDCK) cells were analyzed to determine the sources of diradylglycerols generated during cell growth and phorbol ester stimulation. MDCK cells in log phase growth contained higher levels of diacylglycerol and alkylacylglycerol than confluent cells. Both subclasses of diradylglycerol showed higher levels of saturated and monoenoic species during log phase. Glycerol incorporation into diradylglycerols was increased during growth, consistent with an increase in their synthesis de novo. Stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of protein kinase C, caused an increase in the level of diacylglycerol but not alkylacylglycerol. Log phase MDCK cells showed a greater response to TPA treatment than confluent cells. The molecular species of diacylglycerol generated during stimulation with either TPA or dioctanoylglycerol closely resembled the species of phosphatidylcholine. These results indicate that TPA and synthetic diacylglycerol stimulate endogenous diacylglycerol production through the hydrolysis of phosphatidylcholine. In contrast, the higher content of diacylglycerol and alkylacylglycerol in replicating MDCK cells is the result of an increase in their synthesis de novo.
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Regulation of Folate Receptor Raft RecyclingElnakat, Hala 14 April 2007 (has links)
No description available.
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Papel da proteína quinase C (PKC) na modulação da isoforma 1 do permutador Na+ - H+ (NHE1), em células MDCK. / Role of PKC on exchanger isoform 1 (NHE1), modulation in MDCK cells.Figueiredo, Claudia Ferreira dos Santos Ruiz 31 March 2008 (has links)
O presente trabalho visa contribuir para o esclarecimento da seqüência de eventos intracelulares produzidos pelas PKCs a e e, na modulação do pHi, via NHE1. Os estudos foram realizados em células MDCK e as medidas de pHi efetuadas por microscopia de fluorescência. A expressão das PKCs a e e, bem como do NHE1 foi investigada por western blot, utilizando anticorpos específicos para cada proteína. Os estudos foram realizados na situação controle ou na vigência de PMA ou ANG II, AVP e /ou inibidores específicos para cada receptor hormonal ou isoforma de PKC. Nossos resultados indicam que PMA (10-7 M) estimula a recuperação do pHi, por modular a atividade das PKCs a e e. ANG II e AVP em concentrações fisiológicas estimulam a recuperação do pHi após sobrecarga ácida, concomitante com o aumento da fosforilação da PKC a. Em concentração elevada, ambos hormônios não alteram estes parâmetros. O efeito de ANG II ou de AVP depende da interação de cada hormônio com receptores específicos para modular as vias de sinalização celular envolvidas com o aumento dos níveis de diacilglicerol, cálcio citosólico e AMPc. / The purpose of this work was to investigate the signaling events of PKCs a e e on the NHE1 activity. The effect of phorbol 12-myristate 13-acetate (PMA), angiotensin II (ANG II) or arginine vasopressin (AVP) on the intracellular pH (pHi) was investigated in MDCK cells by using the fluorescence microscopy and fluorescent probe BCECF/AM. The NHE1 or PKCs a e e expression was examined by western blot and specific antibodies. Our results indicate that PMA (10-7 M) or low concentration of ANG II and AVP induced a significant increase of pH recovery rate and PKC a expression, after intracellular acidification with NH4Cl pulse. ANG II or AVP did not change the PKC a expression. However, in right concentration, both hormones did not change these parameter. In conclusion, the effect of ANG II and AVP on NHE1 activity, depend of specifics membrane receptors and cellular signaling of intracellular calcium, DAG and PKCs a and e.
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Papel da proteína quinase C (PKC) na modulação da isoforma 1 do permutador Na+ - H+ (NHE1), em células MDCK. / Role of PKC on exchanger isoform 1 (NHE1), modulation in MDCK cells.Claudia Ferreira dos Santos Ruiz Figueiredo 31 March 2008 (has links)
O presente trabalho visa contribuir para o esclarecimento da seqüência de eventos intracelulares produzidos pelas PKCs a e e, na modulação do pHi, via NHE1. Os estudos foram realizados em células MDCK e as medidas de pHi efetuadas por microscopia de fluorescência. A expressão das PKCs a e e, bem como do NHE1 foi investigada por western blot, utilizando anticorpos específicos para cada proteína. Os estudos foram realizados na situação controle ou na vigência de PMA ou ANG II, AVP e /ou inibidores específicos para cada receptor hormonal ou isoforma de PKC. Nossos resultados indicam que PMA (10-7 M) estimula a recuperação do pHi, por modular a atividade das PKCs a e e. ANG II e AVP em concentrações fisiológicas estimulam a recuperação do pHi após sobrecarga ácida, concomitante com o aumento da fosforilação da PKC a. Em concentração elevada, ambos hormônios não alteram estes parâmetros. O efeito de ANG II ou de AVP depende da interação de cada hormônio com receptores específicos para modular as vias de sinalização celular envolvidas com o aumento dos níveis de diacilglicerol, cálcio citosólico e AMPc. / The purpose of this work was to investigate the signaling events of PKCs a e e on the NHE1 activity. The effect of phorbol 12-myristate 13-acetate (PMA), angiotensin II (ANG II) or arginine vasopressin (AVP) on the intracellular pH (pHi) was investigated in MDCK cells by using the fluorescence microscopy and fluorescent probe BCECF/AM. The NHE1 or PKCs a e e expression was examined by western blot and specific antibodies. Our results indicate that PMA (10-7 M) or low concentration of ANG II and AVP induced a significant increase of pH recovery rate and PKC a expression, after intracellular acidification with NH4Cl pulse. ANG II or AVP did not change the PKC a expression. However, in right concentration, both hormones did not change these parameter. In conclusion, the effect of ANG II and AVP on NHE1 activity, depend of specifics membrane receptors and cellular signaling of intracellular calcium, DAG and PKCs a and e.
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Inhibition of Phorbol Ester-Stimulated Arachidonic Acid Release by AlkylglycerolsRobinson, Mitchell, Burdine, Robin, Warne, Thomas R. 09 February 1995 (has links)
Although synthetic analogs of alkylglycerol (AG), such as dodecylglycerol, possess potent biological activities, their mechanism of action has not been determined. We recently detected substantial amounts of AG in unstimulated MDCK cells (Warne, T.R. and Robinson, M. (1991) Anal. Biochem. 198, 302-307) raising the possibility mediator. In this study, we examined the effects of synthetic AG on the release of arachidonic acid and arachidonate metabolites (AA) from Madin Darby canine kidney (MDCK) cells in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) in order to characterize its effects on this signalling pathway. Treatment of MDCK with AG potently inhibited the release of AA during subsequent stimulation with TPA. Dodecylglycerol, the most effective of a series of alkylgycerols tested, was active at concentrations as low as 3 μM. The sn-1 and sn-3 forms of AG were found to be equally potent inhibitors. The effects of AG on AA release were not the result of arachidonic acid redistribution among cellular lipids and were independent of the phospholipid source of the released AA. AG did not inhibit the release of AA from MDCK cells when bradykinin was used as a stimulus, indicating selectivity for the effects produced by phorbol esters. These results show that AG can function as a potent and specific inhibitor of TPA-mediated AA release. The ability of AG to regulate this signalling pathway in intact MDCK cells, together with its natural occurrence, suggests a potential bioregulatory role for the endogenous compound as an inhibitor of protein kinase C.
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Preconditioning of Isolated Rabbit Cardiomyocytes: Effects of Glycolytic Blockade, Phorbol Esters, and IschaemiaArmstrong, Stephen, Ganote, Charles E. 01 January 1994 (has links)
Objective: The aim was to discriminate among several hypotheses of preconditioning of isolated rabbit cardiomyocytes and to determine if ischaemic preincubation would evoke a protective response. Methods: Isolated myocytes were subjected to 5 min of preincubation, in the presence or absence of glucose, and incubated in the presence of 1 mM iodoacetic acid during the final sustained ischaemic period. In a second series, the protein kinase C (PKC) activators phorbol 12-myristate 13-acetate (PMA), ingenol 3, 20-dibenzoate, and thymeleatoxin were added during preincubation. In a third series, preincubation periods were substituted by brief ischaemic pelleting of cells. Final prolonged ischaemic pelleting was preceded by a 30 min postincubation period. Rate and extent of injury was determined by sequential sampling and assessment of trypan blue permeability following 85 mOsM swelling. Results: Myocytes were preconditioned by a 5 min glucose-free preincubation. Addition of iodoacetic acid into the final ischaemic pellet increased the rates of rigor contracture and injury, but did not abolish the protective response. Direct protein kinase C activation with PMA, a non-selective phorbol ester, and ingenol, an ε, δ-PKC isozyme selective activator, protected cells, but thymeleatoxin, an α,β,γ-PKC isozyme selective activator, did not. A 10 min ischaemic preincubation preconditioned, but the protection was not enhanced when ischaemia was extended to 30 min, or when PMA was included during the initial ischaemic preincubation. Adenosine partially inhibited the response. Conclusions: (1) Preconditioning of isolated myocytes is not dependent on glycolysis or glucose transport. (2) Preconditioning appears dependent on activation of the ε-PKC isoformn. (3) Ischaemia is capable of preconditioning isolated myocytes in vitro, and initiation of this effect is modified by simultaneous additional of adenosine but not by direct protein kinase C activation with PMA. Induction of protection by PMA and ingenol shows that protection requires protein kinase C activation, but direct potassium channel activation by regulatory G proteins is not critical.Cardiovascular Research 1994;28:1700-1706.
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