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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
91

Μελέτη της έκφρασης των φωσφορυλιωμένων μορφών της Hsp27 σε μονοπύρηνα κύτταρα περιφερικού αίματος υγιών ενηλίκων

Βούρτση, Αγγελική 12 December 2008 (has links)
Οι Heat Shock Proteins (Hsps) αποτελούν πολλές διαφορετικές οικογένειες που επάγονται προς απάντηση μιας ευρείας σειράς φυσιολογικών και περιβαλλοντικών ερεθισμάτων. Μια τέτοια πρωτεΐνη, η οποία επάγεται ιδιαίτερα κατά τη διάρκεια της απάντησης σε stress, είναι η Hsp27, με ΜΒ:27kDa, της οποίας η έκφραση φαίνεται να σχετίζεται με αυξημένη επιβίωση των κυττάρων όταν επιδρούν σε αυτά κυτταροτοξικά ερεθίσματα. Έχει φανεί ότι εμποδίζει τον κυτταρικό θάνατο μέσω αλληλεπίδρασης με ποικιλία παραγόντων που προκαλούν απόπτωση. Η Hsp27 είναι μια μοριακή πρωτεΐνη chaperone με ικανότητα να αλληλεπιδρά με μεγάλο αριθμό πρωτεϊνών. Πρόσφατα στοιχεία έχουν δείξει ότι η Hsp27 ρυθμίζει την απόπτωση, χάρη στην ικανότητα που έχει να διαντιδρά με μόρια ¨κλειδιά¨ στο μονοπάτι μεταβίβασης σημάτων της απόπτωσης και ιδιαίτερα, με εκείνα που ενέχονται στην ενεργοποίηση των κασπασών. Οι άλλοι δυο ρόλοι της Hsp27 κατά τη διάρκεια του stress που αποσκοπούν στην κυτταροπροστασία, είναι αφενός να αλληλεπιδρά και να σταθεροποιεί τον κυτταροσκελετό, αφετέρου να ρυθμίζει το ενδοκυττάριο επίπεδο των τοξικών ριζών οξυγόνου. Όταν τα κύτταρα βρίσκονται σε stress τα επίπεδα της Hsp27 είναι γενικώς χαμηλά και αυτή υπάρχει κυρίως με τη μορφή μεγάλων ολιγομερών. Κατά τη διάρκεια της απάντησης στο stress έχουμε αύξηση στα επίπεδα έκφρασης της Hsp27, που συνδυάζεται με μια αναδιοργάνωσή της λόγω φωσφορυλίωσης. Η φωσφορυλίωση μπορεί να συμβεί σε τρεις διαφορετικές θέσεις που εντοπίζονται σερίνες (Ser15, Ser78, Ser82). Η φωσφορυλίωση της Hsp27 καταλήγει σε ανακατανομή των μεγάλων ολιγομερών σε μικρότερα σύμπλοκα. ΣΚΟΠΟΣ: Αντικείμενο της μελέτης μας είναι ακριβώς η έκφραση των φωσφορυλιωμένων μορφών της Hsp27 με μονοπύρηνα κύτταρα περιφερικού αίματος φυσιολογικών ενηλίκων και οι διαφορές που εμφανίζονται όταν τα κύτταρα βρίσκονται in vitro σε βασικές συνθήκες, σε συνθήκες επίδρασης θερμικού stress και σε συνθήκες επίδρασης του παράγοντα TNF-a. ΥΛΙΚΑ ΚΑΙ ΜΕΘΟΔΟΙ: Εφαρμόστηκε η τεχνική της SDS-PAGE ηλεκτροφόρησης και επακόλουθα της WESTERN BLOTTING για την ανίχνευση των πρωτεϊνών. Τα πρώτα πειράματα πραγματοποιήθηκαν σε πρωτεϊνικό εκχύλισμα της κυτταρικής σειράς λευχαιμικών κυττάρων U937 με και χωρίς τη χορήγηση Doxorubicin.Τα επόμενα πειράματα πραγματοποιήθηκαν σε εκχύλισμα πρωτεϊνών μονοπύρηνων κυττάρων περιφερικού αίματος προελεύσεως από ένα τυχαίο δείγμα 6 ενηλίκων ανδρών-γυναικών ηλικίας από 20-30 ετών. Τα τελευταία πειράματα πραγματοποιήθηκαν σε πρωτεϊνικό εκχύλισμα μονοπύρηνων κυττάρων περιφερικού αίματος, το οποίο προερχόταν από ένα τυχαίο δείγμα 7 φυσιολογικών ανδρών-γυναικών ηλικίας 20-30 ετών. Τα κύτταρα αυτά είχαν χωριστεί σε τρεις υποπληθυσμούς ανάλογα με τις συνθήκες που είχαν υποβληθεί: βασικές συνθήκες, συνθήκες επίδρασης θερμικού stress και συνθήκες επίδρασης TNF-a. Ο αρχικός διαχωρισμός των μονοπύρηνων κυττάρων περιφερικού αίματος έγινε με Ficoll. ΑΠΟΤΕΛΕΣΜΑΤΑ: Τα πρώτα πειράματα έγιναν σε πρωτεϊνικό εκχύλισμα κυττάρων της σειράς U937 τα οποία είχαν δεχθεί την επίδραση TNF-a. Η Western Blotting ανάλυση ανέδειξε την παρουσία φωσφορυλιωμένης Hsp27 για τη θέση Ser78,αλλά όχι για τις θέσεις Ser15 και Ser 82. Όταν όμως η ίδια μελέτη πραγματοποιήθηκε σε πρωτεϊνικό εκχύλισμα της ίδιας σειράς που είχαν δεχθεί την επίδραση Doxorubicin αναδείχθηκε η παρουσία φωσφορυλιωμένης Hsp27 για τις θέσεις Ser15 και Ser82. Τα πειράματα που πραγματοποιήθηκαν σε πρωτεϊνικό εκχύλισμα μονοπύρηνων κυττάρων υγιών ενηλίκων, τα οποία δεν είχαν υποστεί απολύτως καμμία επίδραση, ανέδειξαν την παρουσία και των τριών μορφών φωσφορυλιωμένης Hsp27 καθώς και της ολικής μη φωσφορυλιωμένης μορφής σε όλα τα δείγματα. Στα τελευταία πειράματα που έγιναν σε πρωτεϊνικό εκχύλισμα μονοπύρηνων κυττάρων περιφερικού αίματος -που είχαν διαιρεθεί σε τρεις πληθυσμούς ανάλογα με τις συνθήκες που είχαν επιδράσει- ανέδειξαν τα εξής: Η φωσφορυλιωμένη μορφή της Hsp27 για τη θέση Ser78 και τη θέση Ser82 επαγόταν και στους τρεις υποπληθυσμούς κυττάρων, δηλαδή όταν αυτά βρισκόντουσαν υπό βασικές συνθήκες, υπό συνθήκες θερμικού shock και υπό συνθήκες επίδρασης TNF-a. Όσον αφορά τη φωσφορυλιωμένη μορφή της Hsp27 για τη θέση Ser15 διαπιστώθηκε ότι επαγόταν περισσότερο η έκφρασή της σε συνθήκες επίδρασης TNF-a και θερμικού shock από ότι στις βασικές συνθήκες. Η ολική Hsp27, η μη φωσφορυλιωμένη, δεν αναδείχθηκε σε κανέναν από τους τρεις υποπληθυσμούς κυττάρων, σε όσα πειράματα πραγματοποιήθηκαν. ΣΥΖΗΤΗΣΗ: Από τα αποτελέσματα των πρώτων πειραμάτων στα κύτταρα της σειράς U937 προέκυψε η βάσιμη υποψία ότι η επίδραση κάποιου στρεσσογόνου παράγοντα είχε διαφορετική επίδραση στην Hsp27,ανάλογα με το ποιος ήταν αυτός και για πόσο διάστημα επιδρούσε. Επομένως σε διάφορες συνθήκες ανευρίσκονται διαφορετικοί συνδυασμοί της Hsp27, γιατί ακριβώς εξυπηρετούν τις απαιτούμενες διαφορετικές, ενδεχομένως, λειτουργίες αντίστοιχα. Η παρουσία όλων των μορφών της Hsp27 στα μονοπύρηνα κύτταρα περιφερικού αίματος υγιών ενηλίκων όταν αυτά δεν είχαν υποστεί καμμία εξωγενή επίδραση, οδήγησε στο συμπέρασμα ότι ενδεχομένως όλες αυτές οι μορφές της πρωτεΐνης να βρίσκονται σε μια δυναμική κατάσταση εναλλαγής στα κύτταρα ανάλογα με τις ενδογενείς επιδράσεις που δέχονται ανά πάσα στιγμή. Τέλος ,η παρουσία των φωσφορυλιωμένων μορφών της Hsp27 μόνο για τις θέσεις Ser78 και Ser82 σε βασικές συνθήκες αποτελεί σημαντική ένδειξη ότι σε αυτήν την περίπτωση επάγονται περισσότερο τα μεγάλα ολιγομερή της πρωτεΐνης. Αντίθετα, σε συνθήκες επίδρασης θερμικού shock και TNF-a, επάγονται και τα μικρότερα σύμπλοκα της Hsp27, αφού ανευρίσκεται επιπλέον και η φωσφορυλιωμένη μορφή της και για τη θέση Ser15. / -
92

Activation of Immune System Function Against Cancer by Heat Shock Proteins

Kislin, Kerri January 2006 (has links)
Chaperone proteins such as heat-shock proteins 70, 90 and 110, glucose-related protein 94 and calreticulin have been reported to be effective anti-tumor vaccines when purified from a tumor source. We have developed a procedure utilizing a free-solution-isoelectric focusing technique to obtain vaccines from tumor or normal tissue sources that are rich in multiple immunogenic chaperone proteins, called Chaperone-Rich Cell Lysate (CRCL). Tumor-associated peptides are presumed to be the currency of T-cell mediated anti-cancer immunity, and tumor-derived chaperone vaccines are believed to be purveyors of such peptides. As a novel anti-cancer strategy, we have examined the extent to which the peptide repertoire of CRCL can be manipulated. Here, we explored the concept of creating a designer CRCL, utilizing the adjuvant properties and the carrying capacity of CRCL to deliver exogenous antigenic peptides for DC-based presentation and ultimately demonstrate the anti-tumor efficacy of the designer vaccine in vivo. Designer CRCL allows for the development of personalized vaccines to those afflicted with cancer expressing known antigens.Growing evidence indicates that the stress response, specifically involving HSPs, has a profound impact on tumor immunogenicity. Enhancement of T-cell-mediated immunogenicity correlates with the expression of inducible heat shock protein 70 (iHSP70), the major heat-inducible member of the HSP70 family. In addition, studies have shown tumor-specific cell surface localization of iHSP70 correlates with an increased sensitivity to lysis mediated by human natural killer (NK) cells. Given these findings, investigating novel and effective means of modulating the heat shock response within tumor cells may bear great therapeutic potential and result in potent anti-tumor immune activity. Withaferin A (WA) is a compound isolated from the plant Withania somnifera that has been shown to induce a robust transcriptional heat shock response. In our studies, we found that WA treatment resulted in increased surface expression of iHSP70 in several tumor types leading to significant immunostimulatory effects. These findings indicated that WA-dependent modulation of the heat shock response may enhance tumor immunogenicity. Given the potent immunomodulatory and anti-tumor effects of WA as well as the adjuvanticity and specificity of peptide-complexed CRCL against tumors, these therapies individually have shown profound anti-cancer activity.
93

Effect of combined sodium arsenite and cadmium chloride treatment on heat shock protein gene expression in Xenopus laevis A6 kidney epithelial cells

Khamis, Imran 03 September 2013 (has links)
Sodium arsenite and cadmium chloride are two widespread environmental toxicants which have deleterious effects on living organisms. At the cellular level, sodium arsenite and cadmium chloride cause oxidative stress, dysregulation of gene expression, apoptosis, and the unfolding of protein. Furthermore, both chemical stressors individually have the ability to induce heat shock protein (HSP) accumulation. HSPs are molecular chaperones that aid in protein folding, translocation and in preventing stress-induced protein aggregation. Previously, our laboratory demonstrated that treatment of A6 kidney epithelial cells of the frog Xenopus laevis, with either cadmium chloride or sodium arsenite plus a concurrent mild heat shock resulted in an enhanced accumulation of HSPs that was greater than found with the sum of the individual stressors. To the best of our knowledge, no information is available to date on the effect that these two chemical stressors have in combination on HSP accumulation in aquatic organisms. The present study examined the effect of simultaneous sodium arsenite and cadmium chloride treatment on the pattern of HSP30 and HSP70 accumulation in Xenopus A6 cells. Immunoblot analysis revealed that the relative levels of HSP30 and HSP70 accumulation in A6 cells treated concurrently with sodium arsenite and cadmium chloride for 12 h were significantly higher than the sum of HSP30 or HSP70 accumulation from cells subjected to the treatments individually. For instance, the combined 10 µM sodium arsenite plus 100 µM cadmium chloride treatment resulted in a 3.5 fold increase in HSP30 accumulation and a 2.5 fold increase in HSP70 accumulation compared to the sum of the stressors individually. This finding suggested a synergistic action between the two stressors. Pretreatment of cells with KNK437, an HSF1 inhibitor, inhibited the combined sodium arsenite- and cadmium chloride-induced accumulation of HSP30 and HSP70 suggesting that this accumulation of HSPs may be regulated, at least in part, at the level of transcription. Immunocytochemical analysis employing the use of laser scanning confocal microscopy (LSCM) revealed that simultaneous treatment of cells with the two stressors induced HSP30 accumulation primarily in the cytoplasm in a punctate pattern with some dysregulation of F-actin structure. Increased ubiquitinated protein accumulation was observed with combined 10 µM sodium arsenite and 10, 50 or 100 µM cadmium chloride treatment compared to individual stressors suggesting an impairment of the ubiquitin-proteasome degradation system. Finally, while incubation of A6 cells with 1 µM sodium arsenite plus 10 µM cadmium chloride did not induce a detectable accumulation of HSPs, the addition of a 30 °C mild heat shock resulted in a strong accumulation of HSP30 and HSP70. This study has demonstrated that concurrent sodium arsenite and cadmium chloride treatment can enhance HSP accumulation. Since HSP accumulation is triggered by proteotoxic stress, these findings are relevant given the fact that aquatic amphibians in their natural habitat may be exposed to multiple chemical stressors simultaneously.
94

Sex differences in the induced expression of Hsp70 and Hsp27 in the brain and heart of rats

Rioux, Danielle 11 February 2013 (has links)
There are sex differences in degenerative disease prevalence in humans. Most models of degenerative disease use male animals. Examining female and male responses to stress may give insight into disease prevalence. Heat shock proteins are chaperones linked to damaged proteins in degenerative diseases and may be expressed differentially in females and males. My goal was to characterize the induced expression of Hsp70 and Hsp27 in the brain and heart of female and male rats. Rats were heat shocked, brains and hearts were removed 24 hours after, and western analyses were done to quantify the expression of these proteins. Immunofluorescence was used to localize Hsp70 and Hsp27 in the hippocampus. Overall, male rats have significantly greater induced expression of both Hsp70 and Hsp27 in the brain. In the hippocampus, Hsp70 was localized in blood vessels and microglia, and Hsp27 was localized in astrocytes, following heat shock.
95

A Comparison of Heat Shock Protein Expression in Rat Skeletal Muscle After Lengthening or Shortening Contractions

Holwerda, Andrew 27 November 2013 (has links)
The mechanism and subsequent patterns of Heat shock protein (Hsp) expression in skeletal muscle specific to contraction type was determined. Rat tibialis anterior (TA) muscle was forcibly lengthened (LC) or shortened (SC) in 5 sets of 20 repetitions before being removed at 2, 8, 24, 48, 72, or 168 hours and analyzed for muscle damage and Hsp25 and Hsp72 expression. Isometric peak torque was reduced to 63% and 33% (P<0.001) at 3-minutes after SC and LC, respectively. Muscle fibre damage appeared at 8h and beyond following LCs, but no damage was observed after SCs. Hsp25 content in LC muscle increased by 3.1±0.53 fold (P<0.01) at 48h and remained elevated. Hsp72 content increased by 3.8±0.66 fold at 24h and remained elevated. Neither Hsp25 nor Hsp72 content was elevated following SCs. Muscle damage associated with LCs results in a greater Hsp accumulation than SCs and 100 SCs do not result in increased Hsp content.
96

A Comparison of Heat Shock Protein Expression in Rat Skeletal Muscle After Lengthening or Shortening Contractions

Holwerda, Andrew 27 November 2013 (has links)
The mechanism and subsequent patterns of Heat shock protein (Hsp) expression in skeletal muscle specific to contraction type was determined. Rat tibialis anterior (TA) muscle was forcibly lengthened (LC) or shortened (SC) in 5 sets of 20 repetitions before being removed at 2, 8, 24, 48, 72, or 168 hours and analyzed for muscle damage and Hsp25 and Hsp72 expression. Isometric peak torque was reduced to 63% and 33% (P<0.001) at 3-minutes after SC and LC, respectively. Muscle fibre damage appeared at 8h and beyond following LCs, but no damage was observed after SCs. Hsp25 content in LC muscle increased by 3.1±0.53 fold (P<0.01) at 48h and remained elevated. Hsp72 content increased by 3.8±0.66 fold at 24h and remained elevated. Neither Hsp25 nor Hsp72 content was elevated following SCs. Muscle damage associated with LCs results in a greater Hsp accumulation than SCs and 100 SCs do not result in increased Hsp content.
97

Heat shock proteins : interactions with bone and immune cells

Davies, Emma Louise January 2004 (has links)
Heat shock proteins (Hsps) are increasingly being seen as having roles other than those of intracellular molecular chaperones, particularly with regard to their potential to act as cytokines, and to stimulate the innate immune system. Hsps have also been found to promote bone resorption and osteoclast formation in vitro, although the mechanism has not been previously identified. The overall aims of this thesis were to determine whether Hsps could stimulate bone resorption by affecting the RANKL/OPG pathway, and to address the hypothesis that Hsps can act as a danger signal to the innate immune system. In order for Hsps to affect either the RANKL/OPG system of bone resorption or act as danger signals they would need to be actively released from cells, ideally in a controlled manner following exposure to the source of stress. Hsp60 and Hsp70 were found to be released from a range of immune cells including the cell lines Jurkat and U937, and also PBMCs, T-cells and B-cells. This release was not due to cell damage. The release of Hsp60 and Hsp70 were downregulated by inhibitors of protein secretion, in particular Hsp70 release was reduced by compounds that inhibited lysosomal pathways and Hsp60 release by classical secretion inhibitors. Hsp60, Hsp70, GroEL and LPS all affected the RANKL/OPG system of bone regulation; OPG production and release was down-regulated in the MG63 and GCT osteoblast-like cell lines following treatment with Hsp60, Hsp70 and LPS, and RANKL expression was upregulated following treatment with Hsp60, Hsp70, GroEL and LPS. This effect on the RANKL/OPG system was found to translate into an effect on osteoclast formation when conditioned media from treated osteoblasts was added to osteoclast precursors in the presence of M-CSF. A range of different factors that affected Hsp release were identified; PHA activation of PBMCs was found to upregulate Hsp60 release from PBMCs. GroEL and LPS caused an upregulation in Hsp70 release from PBMCs and GCT osteoblast like cells, and Hsp70 was found to stimulate Hsp60 release from PBMCs and GCT cells. These responses of Hsp release were used to form a theory of a cascade-like danger signal that may occur when cells are exposed to bacterial infection and which would result in activation of antigen presenting cells via previously identified receptors for Hsps such as CD14/TLR4 or by unidentified pathways. The elevated release of Hsps in response to GroEL and LPS was also identified as a mechanism that could stimulate bone loss during infection or autoimmuniry by affecting the RANKL/OPG system. hi conclusion, Hsp60 and Hsp70 can be released from immune cells under normal conditions, and from both immune and osteoblast-like cells following stimulation with LPS and other Hsps. The observed release responses provide a mechanism through which Hsps can act as danger signals to the innate immune system, and also as promoters of bone resorption via the RANKL/OPG system.
98

Molecular cloning and characterization of a heat-shock induced calmodulin binding protein gene and cDNAs encoding glutamate decarboxylase from tobacco

Dharmasiri, M. A. Nihal January 1995 (has links)
Thesis (Ph. D.)--University of Hawaii at Manoa, 1995. / Includes bibliographical references (leaves 118-133). / Microfiche. / xiii, 133 leaves, bound ill. 29 cm
99

Remifentanil induces delayed cardioprotection in the rat against ischaemic and reperfusion injury via Kappa, delta, mu opioid receptors and inducible heat shock protein 70

Yu, Che-kwan. January 2007 (has links)
Thesis (M. Phil.)--University of Hong Kong, 2008. / Also available in print.
100

Regulation of UV induced apoptosis in human melanocytes /

Bivik, Cecilia, January 2007 (has links)
Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 4 uppsatser.

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