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The SH2-containing inositol polyphosphate 5-phosphatase-2 (SHIP-2) regulates the actin cytoskeletonDyson, Jennifer Maree, 1975- January 2002 (has links)
Abstract not available
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Investigations into Intracellular Thiols of Biological ImportanceHand, Christine Elizabeth January 2007 (has links)
The presence of thiols in living systems is critical for the maintenance of cellular redox homeostasis, the maintenance of protein thiol-disulfide ratios and the protection of cells from reactive oxygen species. In addition to the well studied tripeptide glutathione (γ-Glu-Cys-Gly), a number of compounds have been identified that contribute to these essential cellular roles. Many of these molecules are of great clinical interest due to their essential role in the biochemistry of a number of deadly pathogens, as well as their possible role as therapeutic agents in the treatment of a number of diseases. A series of studies were undertaken using theoretical, chemical and biochemical approaches on a selection of thiols, ergothioneine, the ovothiols and mycothiol, to further our understanding of these necessary biological components.
Ergothioneine is present at significant physiological levels in humans and other mammals; however, a definitive role for this thiol has yet to be determined. It has been implicated in radical scavenging in vivo and shows promise as a therapeutic agent against disease states caused by oxidative damage. Given the clinical importance of this intracellular thiol, further investigation into the behaviour of ergothioneine appeared warranted. A high level theoretical study was performed to determine the thermodynamic driving force behind the instability of the ergothioneine disulfide, as well as the thermodynamics of the reactions of ergothioneine with a selection of biologically relevant reactive oxygen species. These results were compared to those determined for a glutathione model compound, as well as the related ovothiols. The latter are believed to act as hydrogen peroxide scavengers in vivo and are currently under review as possible therapeutics against oxidative damage. The structural differences between the ovothiols and ergothioneine dramatically affect their reactivity and this study investigates the thermodynamic driving forces behind these differences.
Mycothiol is the major thiol found in the Actinomycetales bacteria, which include the causative agent of tuberculosis, and the enzymes which use mycothiol have been identified as important targets for the development of novel antimicrobials. To better understand the in vivo behaviour of mycothiol, a thorough conformational search was performed to determine what, if any, trends exist among the low energy conformers expected to be present in solution. Knowledge of the conformations preferred by mycothiol may aid in the design of substrate-based inhibitors targeted at mycothiol-dependent enzymes. In addition, the efforts towards the identification of a mycothiol-dependent glyoxalase system are described. The glyoxalase system is essential for the detoxification of methylglyoxal, a toxic by-product of glycolysis, and this system would serve as a target for the design of new therapeutics against tuberculosis and other pathogenic Actinomycetales bacteria.
In addition to the study of intracellular thiols, this work details a preliminary theoretical study of the thermodynamics of the phosphorylation of proteinaceous serine residues by inositol pyrophosphates in eukaryotic cell-free extracts. It has been postulated that this observed activity may represent a novel signalling pathway in eukaryotes. This study focused on the effect of inositol pyrophosphate structure and overall charge on the thermodynamics of these reactions. This information should contribute to our understanding of this novel cellular phosphorylation process.
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An investigation of the vibrational spectra of the inositolsWilliams, Robert Mason, January 1977 (has links) (PDF)
Thesis (Ph. D.)--Institute of Paper Chemistry, 1977. / Includes bibliographical references (p. 257-261).
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Caractérisation du co-transporteur Na+/myo-inositol SMIT2 dans les membranes en bordure en brosse de rein de lapin et d’intestin de ratAouameur, Rym 03 1900 (has links)
Le myo-inositol (MI) est un soluté organique impliqué dans diverses
fonctions physiologiques de la cellule dont la signalisation cellulaire. Il est également
un osmolyte compatible reconnu. Trois co-transporteurs de type actif secondaire
responsables de son absorption ont été identifiés. Deux d’entre eux sont couplés au
transport du sodium (SMIT1 et SMIT2) et le troisième est couplé au transport de
protons (HMIT). L’objectif de cette étude a été la caractérisation du transport du MI
par SMIT2 dans des membranes en bordure en brosse (BBMv) issues du rein de
lapin et de l’intestin de rat ainsi qu’après expression dans les ovocytes de Xenopus
laevis. La quantification de l’ARNm de SMIT1 et de SMIT2 dans le rein nous a
appris que SMIT1 est majoritairement présent dans la médullaire alors que SMIT2
est principalement localisé dans le cortex. Ces résultats ont été confirmés par
immunobuvardage en utilisant un anticorps dirigé contre SMIT2. Grâce à l’inhibition
sélective de SMIT1 par le L-Fucose et de SMIT2 par le D-chiro-inositol (DCI), nous
avons démontré que SMIT2 semble le seul responsable du transport luminal de MI
dans le tubule contourné proximal avec un Km de 57 ± 14 µM. Pour ce qui est de
l’intestin, des études de transport de MI radioactif ont démontré une absence de
transport de MI chez le lapin alors que l’intestin de rat présente un transport de MI
très actif. Une quantification par qRT-PCR nous a permis de constater que l’intestin
de lapin ne semble pas posséder les transporteurs de MI nécessaires. Comme pour le
rein, SMIT2 semble le seul transporteur de MI présent au niveau du pôle apical des
entérocytes intestinaux chez le rat. Il est chargé du prélèvement du MI de
l'alimentation avec un Km de 150 ± 40 µM. Les analyses fonctionnelles exécutées sur
SMIT2 de rat en électrophysiologie après expression dans les ovocytes de Xenopus
laevis donnent sensiblement les mêmes résultats que pour les BBMv de rein de lapin
et d’intestin de rat. Dans les ovocytes, SMIT2 présente une grande affinité pour le
MI (270 ± 19 µM) et le DCI (310 ± 60 µM) et aucune affinité pour le L-fucose. Il est
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également très sensible à la phlorizine (16 ± 7 µM). Une seule exception persiste : la
constante d’affinité pour le glucose dans les BBMv d’intestin de rat est 40 fois plus
petite que celle observée sur les ovocytes de Xenopus laevis. Nous avons également
testé la capacité de certains transporteurs de sucre présents à la surface des
membranes apicales des entérocytes à prélever le MI. Vu que l'inhibition de ces
transporteurs (SGLT1 et GLUT5) ne changeait rien au taux de MI radioactif
transporté, nous en avons conclu qu'ils ne sont pas impliqués dans son transport.
Finalement, l’efflux de MI à partir du pôle basolatéral des entérocytes n’est pas
effectué par GLUT2 puisque ce dernier lorsqu'il est exprimé dans des ovocytes, est
incapable de transporter le MI. / Myo-inositol (MI) is an organic solute involved in various aspects of cell
physiology, including cell signaling. It is also known as a compatible osmolyte.
Three secondary active MI cotransporters have been identified; two are Na+-
coupled (SMIT1 and SMIT2) and one is H+-coupled (HMIT). The main aim of this
study was to characterize MI uptake throught SMIT2 as expressed in epithelial
cells and in Xenopus laevis oocytes. In order to achieve the characterization of this
transport system, we used purified brush border membrane vesicles (BBMv)
isolated from rabbit kidney and rat intestine. We first performed a quantification of
mRNA levels in rabbit kidney using real time PCR for both SMIT1 and SMIT2.
We found that SMIT1 is mainly expressed in the renal medulla while SMIT2 is
mainly localized in the renal cortex. This result was confirmed on Western blots
using an antibody raised against SMIT2. Through inhibition studies using selective
substrates for SMIT1 (inhibited by L-fucose) and SMIT2 (inhibited by D-chiroinositol),
we showed that SMIT2 seems to be responsible for all the apical
transport of MI into the proximal convoluted tubule with a Km of 57 ± 14 µM. By
transport studies we established that rabbit intestine seems to lack apical transport
of MI while rat intestine has a very active uptake of this molecule. qRT-PCR
quantification confirmed the absence of MI transporters in rabbit intestine. As for
kidney, SMIT2 seems to be the only transporter responsible for apical MI uptake
in enterocytes with a Km of 150 ± 40 µM. Functional analysis of rat SMIT2
activity, via electrophysiological studies in Xenopus oocytes, demonstrated
similarities to the activities of SMIT2 from rat intestine and rabbit kidney. SMIT2
displays high affinities for MI (270 ± 19 µM), DCI (310 ± 60 µM) and no affinity
for L-fucose. SMIT2 is very sensitive to phlorizin (Pz; 16 ± 7 µM). Although these
functional characteristics essentially confirmed those found in rat intestine, a
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discrepancy exists between the two systems studied. Indeed, the affinity constant
for glucose was approximately 40-fold lower in vesicles than in oocytes. We also
tested the ability of SGLT1 and GLUT5, other sugar transport systems present in
enterocytes apical membranes, to perform MI uptake. Because the inhibition of
these transporters did not alter radiolabeled MI uptake, we concluded that they had
no significant contribution to MI transport in rat intestine. Finally, the basolateral
efflux of MI was not mediated by GLUT2 because when expressed in oocytes, this
transporter was not able to transport MI.
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The hydrolysis of inositol phospholipid in mouse exocrine pancreas / by Karin Anne TennesTennes, Karin Anne January 1984 (has links)
Bibliography: leaves 358-406 / xv, 406 leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, 1985
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Inositol phospholipid turnover and pancreatic exocrine secretion / by Michael Francis CrouchCrouch, Michael Francis January 1985 (has links)
Offprint of an article by the author inserted / Bibliography: leaves 351-384 / 384 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1985
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Synthesis of inositol phosphate glycans /Jaworek, Christine H. January 2000 (has links)
Thesis (Ph.D.)--Tufts University, 2000. / Adviser: Marc d'Alarcao. Submitted to the Dept. of Chemistry. Includes bibliographical references (leaves 262-271). Access restricted to members of the Tufts University community. Also available via the World Wide Web;
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Design and synthesis of inositol phosphate glycan conjugates /Turner, David Ives. January 2004 (has links)
Thesis (Ph.D.)--Tufts University, 2004. / Adviser: Marc d'Alarcao. Submitted to the Dept. of Chemistry. Includes bibliographical references (leaves 114-118). Access restricted to members of the Tufts University community. Also available via the World Wide Web;
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A knowledge-driven multi-locus analysis of multiple sclerosis susceptibilityBush, William Scott. January 1900 (has links)
Thesis (Ph. D. in Human Genetics)--Vanderbilt University, May 2009. / Title from title screen. Includes bibliographical references.
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Genetic approaches to improve drought tolerance of tomato and tobaccoNa, Jong Kuk, January 2005 (has links)
Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xv, 104 p.; also includes graphics (some col.). Includes bibliographical references (p. 93-104). Available online via OhioLINK's ETD Center
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