Tesis sobre el tema "Up-regulation"
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Schrader-Ratchford, Ann Marie. "P2Y₂ nucleotide receptor up-regulation and function in submandibular gland epithelium". Diss., Columbia, Mo. : University of Missouri-Columbia, 2005. http://hdl.handle.net/10355/4189.
Texto completoThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "May 2005" Includes bibliographical references.
Swan, Edward. "The legal development of derivatives trading and regulation up to 1848". Thesis, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300756.
Texto completoMcColgan, Peter. "Structural brain network degeneration and functional up-regulation in Huntington's disease". Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10041942/.
Texto completoLi, Yu-Hsuan. "Competitiveness in Power System Frequency Regulation Markets : Competitive analysis of the FCR-D up regulation market in Sweden". Thesis, KTH, Energiteknik, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-300745.
Texto completoDen växande andelen väderberoende kraftproduktion i det svenska elsystemet utmanar stabiliteten i hela systemet. Därför växer behovet av att öka systemflexibiliteten genom än mer frekvensregleringsresurser. Numera hanteras frekvensreglering främst av vattenkraft, men Svenska kraftnät (Sveriges systemoperatör), öppnar marknaden alltmer för att locka nya deltagare, för att ge mer balanseringskapacitet och för att öka konkurrensen mellan resurser samt för att förstärka marknadsdynamiken. Detta examensarbete undersöker potentialen för fyra olika tekniker för den framtida stödtjänsten uppreglering för frekvenshållningsreserv för störd drift (FCR-D): vattenkraft, vindkraft, batterilagringssystem och laststyrning (konsumtionsminskning). En modell för klarering av FCR-D uppreglering har byggts upp med logisk kostnadsberäkning och volymuppskattning för varje aktör på FCR-D-marknaden. Känslighetsanalys och marknadsklarerings-modellen har genomförts i Python-programvara. Baserat på scenarievalsmetoden ger denna forskning en överblick över den potentiella framtida FCR-D uppregleringsmarknaden med deltagande av nya aktörer. Resultaten visar att tillgängligheten för FCR-D-marknaden för vissa vattenkraftaktörer har minskat genom åren. Vindkraften har den högsta kostnaden bland de studerade teknikerna medan kostnaderna för batterilagringssystem och laststyrning är konkurrenskraftiga. Dessutom har buden från batterilagringssystem och laststyrning under perioder med höga spotpriser större chans att bli accepterade, vilket skapar möjligheter att locka nya aktörer att gå med på marknaden. De nya aktörernas entré kunde ha sänkt genomsnittliga FCR-D klareringspriser med 19,3 till 70,7 % för perioden 2016 till 2020. Slutligen visar volymändringsscenariot att batterilagringssystem och laststyrning -aktörerna kan påverka FCR-D-priset med stigande tillgänglig volym.
Shen, Jianzhong. "Purinergic proliferation of coronary smooth muscle : receptor cloning, up-regulation and signaling /". Free to MU Campus, others may purchase, 2005. http://wwwlib.umi.com/cr/mo/fullcit?p3204628.
Texto completoMohd, Imran Kamalliawati. "Up-regulation of Hedgehog signalling in satellite cells and skeletal muscle regeneration". Thesis, University of Sheffield, 2019. http://etheses.whiterose.ac.uk/22909/.
Texto completoPraski, Alzrigat Lisa. "Constraints on up-regulation of drug efflux in the evolution of ciprofloxacin resistance". Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-320580.
Texto completoMcElroy, Anita K. "The mechanisms and consequences of cyclin E up-regulation in HCMV-infected cells /". Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2000. http://wwwlib.umi.com/cr/ucsd/fullcit?p9988319.
Texto completoWoodford, Darryl Paul. "Regulating online : participant-driven approaches". Thesis, Queensland University of Technology, 2014. https://eprints.qut.edu.au/68800/1/Darryl%20Paul_Woodford_Thesis.pdf.
Texto completoLochmatter, Priska. "Cytokine selection and CD69 up-regulation in the diagnosis of delayed-type drug hypersensitivity". Bern : [s.n.], 2009. http://www.zb.unibe.ch/download/eldiss/09lochmatter_p.pdf.
Texto completoCloskey, R. M. C. "E6/E7 up-regulation of nucleophosmin is important for proliferation and inhibition of differentation". Thesis, Queen's University Belfast, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.517089.
Texto completoHebbard, Lionel Warren [Verfasser]. "Up-regulation of casein-like proteins during rat pancreatic carcinoma progression / Lionel Warren Hebbard". Karlsruhe : KIT-Bibliothek, 1998. http://d-nb.info/1198222018/34.
Texto completoMatsuyama, Tomonori. "Midazolam inhibits the hypoxia-induced up-regulation of erythropoietin in the central nervous system". Kyoto University, 2015. http://hdl.handle.net/2433/202803.
Texto completoBOCCHETTA, Simone. "Up-regulation of the ATP-binding cassette transporter A1 inhibits hepatitis C virus infection". Doctoral thesis, Università del Piemonte Orientale, 2014. http://hdl.handle.net/11579/45964.
Texto completoVolokhov, Rachael N. "Does greater working memory predict greater skill in the up- and down-regulation of positive emotion?" Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1275654132.
Texto completoArmour, Danielle Louise. "Role of 11β-hydroxysteroid dehydrogenase type 2 in protection against inflammation during atherogenesis : studies in the Apoe-/- /11β-HSD2-/- double knockout mouse". Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4431.
Texto completoLarner, Stephen Frank. "Up-regulation and activation of caspase-12 and caspase-7 following traumatic brain injury in rats". [Gainesville, Fla.] : University of Florida, 2004. http://purl.fcla.edu/fcla/etd/UFE0006609.
Texto completoTypescript. Title from title page of source document. Document formatted into pages; contains 139 pages. Includes Vita. Includes bibliographical references.
Chen, Edwin. "Oxidative stress induces up-regulation of elongation factor-1 alpha (EF-1Ã) en route to apoptosis". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0033/MQ64330.pdf.
Texto completoChen, Edwin 1975. "Oxidative stress induces up-regulation of elongation factor-1 alpha (EF-1ℓ) en route to apoptosis". Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=30354.
Texto completoFan, Yan, Ping Chen, Ying Li, Gregory A. Ordway y Meng Yang Zhu. "Effects of Desipramine Treatment on Stress-Induced up-Regulation of Norepinephrine Transporter Expression in Rat Brains". Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/8597.
Texto completoShipley, Lindsey C. BS, Harika MD Balagoni, Janet Lightner, Victoria PhD Palau y Koyamangalath MD Krishnan. "15 Lox 1 Up-regulation and Cytotoxicity with γ-tocotrienol in HCT-116 Colon Cancer Cells". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/154.
Texto completoMaeno, Atsushi. "Up-Regulation of miR-582-5p Regulates Cellular Proliferation of Prostate Cancer Cells Under Androgen-Deprived Conditions". Kyoto University, 2015. http://hdl.handle.net/2433/199165.
Texto completoWilfong, Erin R. "The role of nerve growth factor in neuropeptide up-regulation in trigeminal ganglia neurons following irritant exposure". Morgantown, W. Va. : [West Virginia University Libraries], 2003. http://etd.wvu.edu/templates/showETD.cfm?recnum=3109.
Texto completoTitle from document title page. Document formatted into pages; contains xiii, 82, [148] p. : ill. (some col.). Includes abstract. Includes bibliographical references.
PAL, KOUSTAV. "EXPLORING CHANGES IN HIGHER-ORDER GENOME ORGANISATION DURING THE COORDINATED TRANSCRIPTIONAL UP-REGULATION IN DROSOPHILA DOSAGE COMPENSATION". Doctoral thesis, Università degli Studi di Milano, 2019. http://hdl.handle.net/2434/609010.
Texto completoSchonberger, Robert Brian. "Upregulation of Hypoxia-Inducible Genes in Endothelial Cells to Create Artificial Vasculature". Yale University, 2006. http://ymtdl.med.yale.edu/theses/available/etd-06282006-142557/.
Texto completoZheng, Feihui y 郑斐晖. "Up-regulation of alpha-enolase (ENO1) by HIF-1α in retinal pigment epithelial cells after hypoxic challenge is not involved in the regulation of VEGF secretion". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208585.
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Li, Xiao Yu 1973. "Beta-adrenoreceptor mediated atria specific up-regulation of regulator of G-protein signaling (RGS) 5 in rodent atrium". Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80318.
Texto completoACQUARONE, ERICA. "Synaptic and Memory Dysfunction Induced by Tau Oligomers is Rescued by Up-regulation of the Nitric Oxide Cascade". Doctoral thesis, Università degli studi di Genova, 2019. http://hdl.handle.net/11567/942799.
Texto completoKing, R. Glenn. "On the immunological roles of TLT2 and HSH2". Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2008r/king.pdf.
Texto completoKoops, Marten Derek. "Transcriptional regulation of human nonspecific cross-reacting antigen, a carcinoembryonic antigen gene family member up-regulated in colorectal carcinomas". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0005/MQ44198.pdf.
Texto completoKoops, Marten Derek. "Transcriptional regulation of human nonspecific cross-reacting antigen, a carcinoembryonic antigen gene family member up-regulated in colorectal carcinomas". Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=20829.
Texto completoSchütte, Verena [Verfasser]. "The Mannose receptor induces T cell tolerance via inhibition of CD45 and up‐regulation of CTLA-4 / Verena Schütte". Bonn : Universitäts- und Landesbibliothek Bonn, 2014. http://d-nb.info/1077289448/34.
Texto completoIsobe, Ken-ichi, Masashi Akiyama, Sachiko Ito, Naomi Nishio y Mayu Hara. "Up-regulation of Gr1^+CD11b^+ cell population in the spleen of NaClO-administered mice works to repair skin wounds". Thesis, Biodiscovery, 2012. http://hdl.handle.net/2237/18821.
Texto completoCashman, Adrian Christopher. "Topping up or watering down? : can regulation support sustainability? : the case of the water industry of England and Wales". Thesis, University of Sheffield, 2004. http://etheses.whiterose.ac.uk/12843/.
Texto completoYamanaka, Kenya. "Olprinone Attenuates Excessive Shear Stress Through Up-Regulation of Endothelial Nitric Oxide Synthase in a Rat Excessive Hepatectomy Model". Kyoto University, 2012. http://hdl.handle.net/2433/157435.
Texto completoSaab, Tara K. "Pollution from septic systems, assessing the implementation of Ontario EPA Regulation 358 and the Clean Up Rural Beaches (CURB) program". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ39875.pdf.
Texto completoChang, Yueming. "Investigation of two early events in amyotrophic lateral sclerosis mRNA oxidation and up-regulation of a novel protective factor MSUR1 /". Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1196182155.
Texto completoYamauchi, Ryoko. "Up-regulation of SR-PSOX/CXCL16 and recruitment of CD8[+] T cells in cardiac valves during inflammatory valvular heart disease". Kyoto University, 2004. http://hdl.handle.net/2433/147487.
Texto completoJohnson, Hope N. "From the ground up: An analysis of the international regulation of agriculture using a rights-based approach to food security". Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/99631/6/Hope_Johnson_Thesis.pdf.
Texto completoVERGINELLI, FEDERICA. "Notch signaling involvement in endothelial responses to inflammation: Jagged1 and Notch1 mediate IL-1b iInduced up-regulation of adhesion molecules". Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2010. http://hdl.handle.net/2108/1250.
Texto completoObjective--Notch signaling plays a key role in endothelial determination and homeostasis through Notch 1 and Notch 4 receptors. In endothelial cells (ECs) the TNFa determines the down-regulation of Notch4 and Hes1 and this modulation are associated with the loss of quiescence and the up-regulation of vascular cell adhesion molecules-1 (VCAM-1), This study investigated the regulation of Notch signaling components upon IL-1β induction and their implication in the up-regulation of adhesion molecules. Methods and Results-- We showed that IL-1β induced a strong up-regulation of the Notch ligand Jagged1. Strikingly, while Notch4 activation decreased, Notch1 active form (Notch1ICD) remained constant. The global inhibition of Notch activation through a g-secretase inhibitor resulted in reduction of IL-1β-induced VCAM-1 up-regulation. Moreover, the silencing of Jagged1 partially affected the up-regulation of adhesion molecules induced by IL-1b, and the double silencing of Jagged1 and Notch1 led to a higher reduction of the adhesion molecules expression after IL-1β treatment. Interestingly, Notch1ICD forced expression induced VCAM-1 expression in ECs and increased the up-regulation induced by IL-1β treatment. Chemical inhibition of the NF-kB nuclear translocation induced by IL-1β treatment did not significantly reduce VCAM-1 expression in Notch1ICD expressing cells. Finally, Hes1 over-expression during IL-1β treatment inhibited the up-regulation of adhesion molecules and, concomitantly, repressed Jagged1 trascription, suggesting a negative regulative loop between Notch signaling component. Conclusions--All together our results indicate that, Jagged1 sustains Notch1 activation that specifies the effects of IL-1β. Thus, Notch1 is the most important receptor involved in inflammatory responses of ECs, and its function is, at least in part, NF-kB-dependent.
Dromey, Jasmin Rachel. "Elucidating novel aspects of hypothalamic releasing hormone receptor regulation". University of Western Australia. School of Medicine and Pharmacology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0133.
Texto completoLi, Ling. "Mechanisms Underlying Apoptosis Inhibition and Transcription Repression by Ski". Connect to text online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1118235807.
Texto completoBastien, Jérémie. "Le football professionnel européen dans un système capitaliste financiarisé en crise : une approche régulationniste des facteurs de changement institutionnel". Thesis, Reims, 2017. http://www.theses.fr/2017REIME002/document.
Texto completoEconomists argue that the European professional football is in crisis. This thesis discusses this postulate by testing the relationship between the changes in football and the transformations of modern capitalism. Our methodology is based on a meso-level analysis from the French “Régulation theory” which provides a systemic and multilevel analysis. The thesis thus emphasizes how the progressive integration of financialised interests in football has an influence on the strategies of football traditional stakeholders. It actually shows that the financialisation process of the European professional football leads to growth since the 1980s. However, this growth is rather unstable because losses and indebtedness are part of clubs activity. The incentive for sports performance (open league), the players’ strong bargaining power (hold-up) and the flexibility of the regulatory environment are the main determinants of the clubs’ high spendings. Contrary to the “small” clubs, this situation is not a constraint for the “big” clubs thanks to the financial contributions they obtain from their owners, from their funding partners and from their participation to supranational competitions. In this environment and despite instability, the growth regime remains nevertheless sustainable. The stakeholders create new compromises to reduce imbalances: these compromises are the roots for new institutional arrangements that finally support the growth logic which is in place. There is therefore a “régulation” in European professional football, that is to say a process that contributes to the reproduction of the sector. However, this process paradoxically increases inequalities and may encourage the conditions for a major economic crisis
Yin, Yinfei. "Helicobacter pylori mediated hypergastrinaemia stimulates heparin-binding epidermal growth factor-like growth factor shedding via up-regulation of matrix metalloproteinase-7". Thesis, University of Nottingham, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491023.
Texto completoKraft, Juliane Viktoria [Verfasser] y Sabine [Akademischer Betreuer] Windhorst. "Up-regulation of Biglycan is associated with poor prognosis and PTEN deletionin patients with prostate cancer / Juliane Viktoria Kraft ; Betreuer: Sabine Windhorst". Hamburg : Staats- und Universitätsbibliothek Hamburg, 2019. http://d-nb.info/1181328918/34.
Texto completoFukui, Toshiro. "Gastric mucosal hyperplasia via up-regulation of gastrin induced by persistent activation of gastric innate immunity in MHC class 2-deficient mice". Kyoto University, 2006. http://hdl.handle.net/2433/143866.
Texto completoAguilar, Fenollosa Ernestina. "Efecto de la gestión de la cubierta vegetal en el control biológico de Tetranychus urticae en mandarino clementino". Doctoral thesis, Universitat Jaume I, 2011. http://hdl.handle.net/10803/22694.
Texto completoTetranychus urticae es una especie plaga importante en cítricos que puede también alimentarse de otras especies asociadas a la cubierta vegetal de este cultivo. Para determinar el efecto de la gestión de la cubierta vegetal en el control biológico de este ácaro, hemos estudiado la dinámica tanto de ácaros Tetranychidae como Phytoseiidae en cuatro parcelas comerciales de mandarino clementino en las que se aplicó tres estrategias diferentes de gestión de la cubierta vegetal: (1) suelo desnudo, (2) cubierta espontánea y (3) cubierta sembrada de Festuca arundinacea. Los resultados apuntan a que tanto los enemigos naturales (mecanismos "top-down") como la planta huésped (mecanismos "bottom-up") juegan un papel importante en la regulación de los ácaros Tetranychidae.
Por un lado, la selección de dos razas de T. urticae especializadas en F. arundinacea y en Citrus clementina, en la cubierta y en el árbol respectivamente, cuando esta gramínea se utiliza como cubierta podría explicar en parte los resultados obtenidos (regulación "bottom-up") ya que esto impediría a los especímenes de una planta huésped colonizar con éxito la otra. Los ensayos de trasplante recíproco realizados muestran que las dos demos de T. urticae recogidas de clementina y F. arundinacea difieren considerablemente en su éxito en el desarrollo en el huésped alternativo y esto indica la existencia de fenómenos de adaptación local.
Esta adaptación se traduciría en mecanismos "bottom-up" que evitarían que los ácaros que habitan en la cubierta colonicen con éxito la copa de los árboles.
Por otro lado, la composición cualitativa de las comunidades de Phytoseiidae asociados a las diferentes cubiertas podría ser clave en la regulación de las poblaciones de T. urticae y Panonychus citri (regulación "top-down"). Los ácaros Phytoseiidae tipo I y II, depredadores especializados en Tetranychidae, se encuentran de manera consistente en la cubierta de F. arundinacea y esto puede explicar la mejor regulación de las poblaciones de ácaros Tetranychidae en los árboles asociados a esta cubierta. Por el contrario, la disposición más regular de fuentes de alimentación alternativas (polen) en la cubierta natural en relación con la cubierta de F. arundinacea, podría explicar la mayor abundancia de Phytoseiidae tipo IV en la primera. Como consecuencia, los Phytoseiidae tipo I y II, más eficaces en el control de Tetranychidae, podrían sufrir las consecuencias de ser competitivamente inferiores que el Phytoseiidae generalista tipo IV que explota el polen en la cubierta espontánea. Este hecho, en combinación con los períodos de escasez de presa, podría dar lugar a su desaparición del agroecosistema y resultar en un deficiente control de los ácaros Tetranychidae en los árboles asociados a una cubierta natural.
Haciendo balance de gastos e ingresos, la cubierta más favorable fue la de F. arundinacea (entre 44,4 y 74,5% de reducción de costes en relación con la más cara). Festuca arundinacea como cubierta vegetal es una estrategia de control biológico por conservación muy recomendable para los productores de clementina. Aunque su uso no redujo las poblaciones de ácaros en los árboles por debajo del umbral económico, la disminución en la necesidad de tratamientos, hace que la adopción de esta táctica sea una alternativa beneficiosa tanto ecológica como económicamente.
Nuestros resultados apuntan a la cubierta de F. arundinacea, que no permitió el establecimiento de Tetranychus evansi y ofrece una mejor regulación de P. citri y T. urticae que en suelo desnudo o cubierta natural, como la más adecuada para un control más sostenible de los ácaros Tetranychidae en cítricos.
Domingues, Rita B. "Bottom-up regulation of phytoplankton in the Guadiana estuary". Doctoral thesis, 2010. http://hdl.handle.net/10400.1/1558.
Texto completoPhytoplankton are key players in the aquatic environment and they can be effectively used to understand and predict the functioning and production of aquatic ecosystems. Given that phytoplankton is affected by natural and human-induced perturbations, such as eutrophication and global climate change, it is pressing to understand which factors regulate phytoplankton communities. The main goal of this work was, therefore, to understand how phytoplankton growth and production in the turbid Guadiana estuary, particularly in the freshwater tidal zone, is regulated by bottom-up factors, namely nutrients and light. Enrichment bioassays were carried out to evaluate nutrient and light limitation of phytoplankton growth. Nutrient limitation, specifically by nitrogen, was observed during the productive period. Nitrogen, as nitrate, became limiting to phytoplankton growth at concentrations lower than 20 WM. Although nitrate was the main nitrogen source in the Guadiana estuary, an overall preference for ammonium was observed, mainly by cyanobacteria and green algae. Diatoms were the most nutrient-limited group, and they clearly preferred nitrate as their N-source. Regarding light availability, phytoplankton was not acclimated to the low light conditions that prevail in the Guadiana estuary and light limitation occurred throughout the year. Diatoms were the most light-limited group, whilst cyanobacteria seemed to be more acclimated to low light. Primary production was higher in the more turbid regions, where light availability was the lowest, but nutrient concentrations, although occasionally limiting, were the highest. Therefore, phytoplankton in such turbid regions were the most efficient in using limiting resources. River flow was a major regulator of nutrient and suspended matter inputs to the estuarine zone. Tidallyinduced variability of phytoplankton and environmental drivers in the freshwater tidal estuarine zone was low and resulted from seasonal and fortnightly variability in river flow and tidal currents.
Fundação para Ciência e Tecnologia (FCT) - 27536/2006)
Shan, Shannon J. C. "Up-regulation of human tissue kallikrein 6 in ovarian cancer". 2006. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=450528&T=F.
Texto completo"Inflammation-induced up-regulation of hepcidin expression in the brain". 2013. http://library.cuhk.edu.hk/record=b5549291.
Texto completo在本研究的第一部分,我們檢測了炎症是否調節腦內鐵調素的表達,以及這種調節作用在腦內是否具有區域特異性。利用脂多糖(一種廣泛使用的炎症誘導劑)誘導的炎症模型,我們發現腦室內注射脂多糖可區域特異性地誘導腦內鐵調素的表達,即誘導皮層和黑質的鐵調素表達,而海馬的鐵調素水準無顯著改變。與此相伴隨的是腦內膜鐵轉運蛋白區域特異性的表達下降。此外,我們發現脂多糖處理引起的腦內鐵調素表達升高發生在神經元而不是星形膠質細胞內。這些發現提示,炎症能夠區域特異性地上調腦內鐵調素表達,上調的鐵調素轉而下調特定腦區膜鐵轉運蛋白的表達。
在本研究的第二部分,我們檢測了離體水準上炎症對原代皮層神經元和MES23.5多巴胺能細胞鐵調素表達的影響。我們觀察了炎症對這些細胞鐵調素和膜鐵轉運蛋白表達的作用。我們發現脂多糖不增加原代皮層神經元鐵調素的表達。但在與BV-2小膠質細胞共培養的條件下,原代皮層神經元的鐵調素表達水準經脂多糖刺激後上升。我們檢測了一系列可能由小膠質釋放的促炎細胞因數對神經元鐵調素表達的影響。結果表明,白介素-6介導了脂多糖誘導的神經元鐵調素表達升高的作用。我們進一步發現,白介素-6在短時間內直接增加神經元鐵調素表達和降低膜鐵轉運蛋白表達。最後我們進一步探究了白介素-6對腦內鐵調素表達的調控機制,發現在原代皮層神經元和MES23.5多巴胺能細胞中白介素-6誘導的鐵調素表達是通過信號轉導和轉錄啟動因數3信號通路介導的。
綜上所述,我們的研究結果表明,炎症在調節腦內鐵調素表達和控制腦內鐵轉運中發揮重要的作用。在腦內,炎症區域特異性地誘導鐵調素表達上調和膜鐵轉運蛋白表達下調。白介素-6/ 信號轉導和轉錄啟動因數3這一信號通路介導了在炎症情況下腦內鐵調素表達。這些發現加強了我們對於腦內鐵調素表達的調節過程的理解,並提供了一種新的關於鐵調素在腦內抗炎作用的治療觀點。
Hepcidin, as the central iron regulatory hormone, plays a key role in maintaining peripheral iron homeostasis. The expression of hepcidin in the periphery is regulated by multiple factors homeostatically, including iron status, inflammation, erythropoietic activity and hypoxia. The presence and widespread distribution of this peptide in the brain suggests that hepcidin may also have an essential role in brain iron homeostasis. In this study we tested the hypothesis that inflammation exerts an important role in the regulation of brain hepcidin expression, which might alter brain iron metabolism.
To investigate whether inflammation could regulate brain hepcidin expression and whether this regulatory role is regionally specific in the brain, in the first part of study, we explored the effects of lipopolysaccharides (LPS), a widely used inflammation-inducing agent, on hepcidin expression in different brain regions of the rat brain in vivo. We found that intracerebroventricular (i.c.v.) injection of LPS induced brain hepcidin expression regionally specifically, that is, in the cortex and substantia nigra but not in the hippocampus. This effect was accompanied by a regionally specific decrease in brain ferroportin expression. Besides, brain hepcidin was found to be increased in neurons but not in astrocytes by LPS treatment. These findings indicate that inflammation could up-regulate brain hepcidin expression regionally specifically in the brain, which in turn down-regulates ferroportin expression in specific brain regions.
In the second part, we investigated the effects of inflammation on hepcidin expression in primary cortical neurons and MES23.5 dopaminergic cells in vitro. The expression of hepcidin as well as ferroportin was observed. We found that LPS did not increase hepcidin expression in primary cortical neurons. However, LPS induced neuronal hepcidin expression with the presence of BV-2 microglia cells. We examined the effects of a series of pro-inflammatory cytokines which could be released by microglia cells, on hepcidin expression, and found that interleukin-6 (IL-6) mediated neuronal hepcidin expression induced by LPS. Furthermore, we found that IL-6 directly increased hepcidin expression and decreased ferroportin expression in an acute manner. Finally, we further investigated the mechanisms underlying the regulatory effects of IL-6 on brain hepcidin expression, and found that IL-6-induced hepcidin expression is via signal transducer and activator of transcription-3 (STAT3) signaling in primary cortical neurons and MES23.5 dopaminergic cells.
In conclusion, the results of the present study implied that inflammation plays an important role in regulating brain hepcidin expression and controlling brain iron transport. In the brain, hepcidin up-regulation and ferroportin down-regulation is induced by inflammation in a regionally specific way. IL-6/ STAT3 signaling pathway is essential for brain hepcidin expression during inflammation. These findings enhance our understanding of the regulatory process of hepcidin in the brain, and provide a new therapeutic perspective of hepcidin in anti-inflammation in the brain.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
He, Xuan.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2013.
Includes bibliographical references (leaves 110-128).
Abstracts also in Chinese.
ABSTRACT OF THESIS ENTITLED --- p.II
ACKNOWLEDGENENTS --- p.VII
TABLE OF CONTENTS --- p.VIII
LIST OF FIGURES --- p.XII
LIST OF ABBREVIATIONS --- p.XV
Chapter CHAPTER 1 --- INTRODUCTION --- p.1
Chapter 1.1 --- Introductory statement --- p.1
Chapter 1.2 --- Hepcidin in the periphery --- p.1
Chapter 1.2.1 --- Biological functions of hepcidin --- p.3
Chapter 1.2.2 --- Regulation of hepcidin synthesis --- p.10
Chapter 1.2.2.1 --- Regulation of hepcidin by iron --- p.10
Chapter 1.2.2.2 --- Regulation of hepcidin by inflammation --- p.17
Chapter 1.2.2.3 --- Regulation of hepcidin by anemia, erythropoiesis and hypoxia --- p.21
Chapter 1.2.3 --- Misregulation of hepcidin --- p.25
Chapter 1.2.3.1 --- Hepcidin deficiency --- p.25
Chapter 1.2.3.2 --- Hepcidin excess --- p.27
Chapter 1.3 --- Hepcidin in the brain --- p.28
Chapter 1.4 --- Neuroinflammation --- p.30
Chapter 1.5 --- Summary --- p.33
Chapter 1.6 --- Objectives . --- p.34
Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.36
Chapter 2.1 --- Animal experiments --- p.36
Chapter 2.1.1 --- Intracerebroventricular LPS injection --- p.36
Chapter 2.1.2 --- Animal sacrifice and sample collection --- p.37
Chapter 2.2 --- Cell cultures --- p.38
Chapter 2.2.1 --- Primary cortical neurons culture --- p.38
Chapter 2.2.2 --- BV-2 microglia cells --- p.39
Chapter 2.2.3 --- MES23.5 dopaminergic cells --- p.39
Chapter 2.3 --- Western blot analysis --- p.40
Chapter 2.4 --- ELISA measurement --- p.42
Chapter 2.5 --- Immunohistochemistry --- p.43
Chapter 2.6 --- Statistical analysis --- p.44
Chapter CHAPTER 3 --- IN VIVO STUDY OF THE EFFECTS OF INFLAMMATION ON BRAIN HEPCIDIN EXPRESSION --- p.46
Chapter 3.1 --- ABSTRACT. --- p.46
Chapter 3.2 --- INTRODUCTION --- p.47
Chapter 3.3 --- MATERIALS AND METHODS --- p.48
Chapter 3.4 --- RESULTS --- p.50
Chapter 3.4.1 --- LPS injection induced hepcidin expression in neurons in the cortex and substantia nigra but not in the hippocampus of the rat brain --- p.50
Chapter 3.4.2 --- LPS injection did not induce hepcidin expression in astrocytes in the cortex, hippocampus and substantia nigra of the rat brain --- p.51
Chapter 3.4.3 --- LPS injection induced hepcidin up-regulation and ferroportin down-regulation in the cortex and substantia nigra but not in the hippocampus of the rat brain --- p.52
Chapter 3.4.4 --- LPS injection induced IL-6 production and STAT3 phosphorylation in the cortex, hippocampus and substantia nigra of the rat brain --- p.53
Chapter 3.5 --- DISCUSSION --- p.54
Chapter CHAPTER 4 --- IN VITRO STUDY OF THE MECHANISMS UNDERLYING THE EFFECTS OF INFLAMMATION ON BRAIN HEPCIDIN EXPRESSION --- p.72
Chapter 4.1 --- ABSTRACT --- p.72
Chapter 4.2 --- INTRODUCTION --- p.73
Chapter 4.3 --- MATERIALS AND METHODS --- p.74
Chapter 4.4 --- RESULTS --- p.76
Chapter 4.4.1 --- IL-6 mediated LPS-induced hepcidin expression in primary cortical neurons with the presence of BV-2 microglia --- p.76
Chapter 4.4.2 --- IL-6 induced hepcidin up-regulation and ferroportin down-regulation in primary cortical neurons in an acute manner --- p.77
Chapter 4.4.3 --- Inhibition of STAT3 activity suppressed IL-6-induced hepcidin up-regulation and ferroportin down-regulation in primary cortical neurons --- p.79
Chapter 4.4.4 --- IL-6 rather than other cytokines induced STAT3 activation in primary cortical neurons --- p.80
Chapter 4.4.5 --- Inhibition of STAT3 activity suppressed IL-6-induced hepcidin up-regulation and ferroportin down-regulation in MES23.5 dopaminergic cells --- p.80
Chapter 4.5 --- DISCUSSION --- p.81
Chapter CHAPTER 5 --- GENERAL DISCUSSION --- p.102
REFERENCE --- p.110