Dissertations / Theses on the topic 'Calcium channel drugs'
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Young, Lois-May. "Evaluation of polycyclic amines as modulators of calcium homeostasis in models of neurodegeneration / Young L." Thesis, North-West University, 2012. http://hdl.handle.net/10394/7591.
Full textThesis (Ph.D. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2012.
Zhang, Changfeng. "Investigation of the endoplsmic reticulum calcium stores for their potential roles in neuroprotection using the NG115-401L neuronal cell line model." Scholarly Commons, 2014. https://scholarlycommons.pacific.edu/uop_etds/142.
Full textRuchala, Iwona. "EXPANDING MONOAMINE TRANSPORTERS PHARMACOLOGY USING CALCIUM CHANNELS." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/5032.
Full textDowell, Margaret Anne. "Influence of three-tier cost sharing on patient compliance with and switching of cardiovascular medications." Columbus, Ohio : Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1030118543.
Full textTitle from first page of PDF file. Document formatted into pages; contains xvi, 173 p.: ill. Includes abstract and vita. Co-advisors: Craig A. Pedersen, Dept. of Pharmacy; Anne Scheck McAlearney, School of Public Health. Includes bibliographical references (p. 169-173).
Herzinger, Thomas Andreas. "Effects of the Cardioprotective Drugs Dexrazoxane and ADR-925 on Doxorubicin Induced Ca2+ Release from the Sarcoplasmic Reticulum." PDXScholar, 1996. https://pdxscholar.library.pdx.edu/open_access_etds/5069.
Full textWhittington, Miles A. "The ethanol withdrawal syndrome : a role for dihydropyridine-sensitive calcium channels in neural hyperexcitability states." Thesis, University of Bristol, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279774.
Full textBrown, Jason Peter. "The novel antiepileptic drug, gabapentin (Neurontin), binds to the α₂δ subunit of a voltage-dependent calcium channel." Thesis, University of Cambridge, 1996. https://www.repository.cam.ac.uk/handle/1810/252157.
Full textFlorent, Romane. "Intérêt de la modulation pharmacologique des voies de signalisation calcique pour restaurer le contrôle de l'apoptose dans les cancers ovariens chimiorésistants Inhibition of store-operated channels by carboxyamidotriazole sensitizes ovarian carcinoma cells to anti-BclxL strategies through Mcl-1 down-regulation Drug Repositioning of the α1-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug? Bim, Puma and Noxa upregulation by Naftopidil sensitizes ovarian cancer to the BH3-mimetic ABT-737 and the MEK inhibitor Trametinib." Thesis, Normandie, 2020. http://www.theses.fr/2020NORMC413.
Full textThe poor prognosis of ovarian cancer is mainly explained by a high rate of resistance to conventional chemotherapy presented by patients. Therefore, discovery of both alternative therapeutic strategies to chemotherapy and predictive biomarkers for response to this treatment represent a major challenge for improving the management of this pathology. Chemoresistance of ovarian cancer cells is mainly due to their resistance to apoptosis, resulting from an imbalance between the pro- and anti-apoptotic members of the Bcl-2 family that control this type of cell death. Thus, all strategies able to modulate the [pro]/[anti-apoptotic] protein ratio in favor of [pro-] effectively restore apoptosis in these cells. However, calcium signaling is known to regulate the expression of these proteins and thus appears to be a relevant target for restoring apoptosis in chemoresistant ovarian cancer cells. In this context, we have shown that three calcium signal modulators are able to induce the death of these cells in association with ABT-737, a BH3-mimetic targeting the activity of the anti-apoptotic Bcl-xL. This sensitization to ABT-737 is enabled by the fact that carboxyamidotriazole represses the expression of the anti apoptotic Mcl-1 via the inhibition of SOCE currents, naftopidil increases pro-apoptotic protein expression via ER stress induction or JNK activation and thapsigargin seems to prepare cell death through increasing intracellular calcium concentration via STIM1 and, maybe, through Noxa expression induction. In addition, players of the calcium signaling toolkit, known to undergo remodeling during carcinogenesis could be proven as tools for predicting response to chemotherapy. In this context, we have shown that the expression of the calcium pump SERCA2 seems to play a role as a predictive biomarker for response to chemotherapy of patients with ovarian cancer
Olah, Mark E. "Effects of calcium channel blockade and intracellular calcium antagonism on endothelium-dependent responses of the isolated rat aorta and influence of the endothelium on drug action /." The Ohio State University, 1988. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487590702989006.
Full textZhang, Yi. "Potential impact of breast cancer resistance protein on drug disposition during pregnancy /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/7970.
Full textSelvey, Christine Enid. "Comparative effects of calcium channel antagonism and beta-1 selective blockade on exercise performance in physically active hypertensive patients." Master's thesis, University of Cape Town, 1997. http://hdl.handle.net/11427/26736.
Full textWynne, Patricia M. "Ethanol Sensitivity and Tolerance of Rat Neuronal BK Channels: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/399.
Full textFeinberg-Zadek, Paula Leslie. "Alcohol Modulation of Human BK Channels Evidence for β-Subunit Dependent Plasticity in Functional Ethanol Tolerance: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/195.
Full textAssadian, Sarah. "Rodent FDG-PET imaging for the pre-clinical assessment of novel glioma therapies." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101836.
Full textLa découverte accélérée de nouvelles molécules thérapeutiques qui ciblent lesmécanismes de progression du cancer tels que l'invasion et l'angiogenèse, nécessite lamise au point et la validation de techniques efficaces qui permettent d'évaluer l'efficacitéthérapeutique de ces agents in vivo. Le développement récent des scanners detomographie à émission de positron (TEP) dédiés à l'imagerie de petits animaux(microPET, CT! Concorde R4), permet aujourd'hui d'obtenir une image fonctionnelle etmoléculaire de haute résolution des modèles rongeurs. Cette étude s'intéresse au potentieldu 18F-2-fluoro-2-deoxyglucose (FDG) en utilisant l'imagerie microPET dansl'évaluation de l'efficacité de nouveaux agents thérapeutiques dans un modèle de gliomechez le. rat. Cette technique pourrait éventuellement mener à une évaluation rapide et àgrande échelle de la réponse tumorale, ainsi que la mesure de l'efficacité d'agentsthérapeutiques in vivo au stade d'étude préclinique. Globalement, cette étude a pour butde faciliter la transition entre la découverte de nouvelles molécules thérapeutiques et leursapplications cliniques.
Chao, Su-Hui, and 趙素慧. "Photosensitivity drugs(I) Photodegradation of calcium channel blockers(II) Photoproducts of NSAIDs and their anti-inflammatory activities." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/89841605521014148399.
Full text臺北醫學大學
藥學研究所
95
Photosensitivity is a commonly adverse effect of drugs. The purpose of the first part of this study is focus on the photodegradation of nicardipine. When nicardipine was exposed to the Hg lamp, eight photoproducts of nicardipine were identification by LC/MS. The main degraded product was a pyridine analogue (NIC-7). Nicardipine apparently undergoes a series of nitro group photo-reduction pathways under irradiation leading to a complex formation of mainly the reduced products. A reaction scheme of nicardipine was proposed. The second part, gives a study on the photochemical behavior when NSAIDs (flurbiprofen and indomethacin) in alcoholic solvents are exposed to Hg lamps. GC/MS and LC/MS were applied to determine the structure of photoproducts. In addition, some pharmacological effects were also examined. In total, ten and four photoproducts derived from flurbiprofen and indomethacin methanolic samples, respectively, were identified by GC/MS and LC/MS. Furthermore, the reaction schemes of flurbiprofen and indomethacin in methanol are proposed. As to the study of pharmacological effects, results suggested that among all the related photoproducts, Indomethacin stand out and showed the strongest hydroxyl radical-scavenging effect with an IC50 of 65 µM and the strongest xanthine oxidase inhibitory effect with an IC50 of 86 µM. We also found that the methyl ester derivatives of indomethacin (IN-3) could more-potently inhibit PGE2 and NO production and iNOS and COX 2 protein expression from LPS-stimulated RAW 264.7 cells than indomethacin, similar to the effect of a typical NSAID. The cytotoxic effects of the test samples were measured using the MTT assay. The results showed that IN-3 with an IC50 value maintained at 36.9 ?慊/mL for 12 h that exhibited stronger cytotoxicity than indomethacin in HL-60 cells. Moreover, IN-3 caused apoptotic bodies, DNA fragmentation, and enhanced PARP and pro-caspase 3 degradation in HL-60 cells as determined by a series of biochemical analyses. The above results indicated that the photoproduct, IN-3, had stronger anti-inflammatory in LPS-stimulated RAW 264.7 cells and cytotoxicity effects in HL-60 cells than the parent drug, indomethacin.
Tong, Clement Tsz-Ming. "Comparison of drug blockade of a neuronal calcium-activated potassium channel with cardiac repolarizing potassium channels by potential class III agents." Thesis, 1994. http://hdl.handle.net/2429/5546.
Full textGuan, Wendy. "Domain II (S5-P) region in Lymnaea T-type calcium channels and its role in determining biophysical properties, ion selectivity and drug sensitivity." Thesis, 2014. http://hdl.handle.net/10012/8507.
Full textMahmoud, Sherif. "Drug-disease interaction: effect of inflammation on the pharmacological response to calcium channel blockers." Phd thesis, 2010. http://hdl.handle.net/10048/1540.
Full textpharmaceutical sciences
"Modulation by extracellular ATP of L-type Calcium channel currents in guinea-pig single sinoatrial nodal cells." 1997. http://library.cuhk.edu.hk/record=b6073002.
Full textThesis (Ph.D.)--Chinese University of Hong Kong, 1997.
Includes bibliographical references (p. 219-256).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Pan, Hung-Fang, and 潘虹方. "Correlation Study between Calcium Channel Antagonists-Macrolides Drug Interaction with Hypotension, Shock and Acute Kidney Injury." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/44812119808367474872.
Full text高雄醫學大學
藥學系碩士在職專班
103
Background: Previous case reports revealed that concomitant therapy with calcium channel blockers and macrolides resulted in hypotension. In 2012, the U.S. FDA issued a warning to remind physicians that the combination of clarithromycin and calcium channel blockers may cause severe hypotension. Drug-drug interactions not only affect the effectiveness, but also cause adverse effects, especially in cardiovascular drugs. Because a lot of cardiovascular drugs are metabolized by cytochrome P450 enzyme systems, simultaneous use with CYP 3A4 inhibitors or inducers, will lead to fluctuations of therapeutic levels, and further resulted in some adverse effects. Contrary to azithromycin, erythromycin and clarithromycin have inhibitory activity of cytochrome P450 3A4 (CYP 3A4). Therefore, co-administration with some calcium channel blockers which are the substrates of CYP 3A4 system will increase the risk of hypotension. Consequently, while hypotension occurs, poor kidney perfusion may also be a concern. Objective: We conducted a population-based cohort study to investigate the incidence of acute kidney injury, hypotension and shock from the possible drug-drug interaction of calcium channel antagonists-macrolides. Methods: The study used the 2005 National Health Insurance Research Database (NHIRD) from 2000 to 2012. We identified patients who had concurrent usage of calcium channel blockers and macrolides in 2002~2012. According to CYP 3A4 inhibitor activity, users of erythromycin/clarithromycin were in the treatment group, and azithromycin users were the control group. The incidences of hypotension, shock, and acute kidney injury after concurrent usage were identified. The propensity scores (PS) weighting were adapted in the statistical analysis. Results: In the period between 2000~2012, those combinations at the same prescription,were frequently prescribed by internists, accounting for 59.37%% of all, and it had more frequency of occurrence in local community hospitals (60.53%) than in the clinic. We also identified 1,774 patients who received a coprescription with calcium channel blockers and macrolides in the period between 2002~2012, including 1,407 patients in erythromycin/clarithromycin group and 367 patients in azithromycin group. The incidence of acute kidney injury in azithromycin group (7.08%) was higher than in erythromycin/ clarithromycin group (3.20%) with odds ratio (OR) of 0.43 (95% CI: 0.26~0.71). But the incidence of hypotension or shock was not statistical significance from the two groups (OR: 0.55, 95% CI: 0.29~1.05). However, in azithromycin group, there were more comorbidities, and more renal disease patients. Therefore, propensity score was used to balance the two groups. In those who had underlying disease with renal disease, the incidence of acute kidney injury outcome in erythromycin/ clarithromycin group was 14.52%, and in azithromycin group was 12.70% (p= 0.73, weighted OR: 1.77, 95% CI: 0.98~3.18). Similarly, incidences of hypotension or shock were respectively 3.23%, 6.35% (p= 0.45, weighted OR: 1.50, 95% CI: 0.61~3.69). Furthermore, in our study, older age, multiple comorbidities, chronic renal disease, and the longer length of combinated days seemed to relate between acute kidney injury in erythromycin/clarithromycin group. Conclusions: The finding did not support the theory that combination with azithromycin would be more risk than erythromycin/clarithromycin group. There was no statistical significance in incidences of hypotension or shock between two groups in 18 years older Taiwanese.
Wang, Xueping. "Properties of drug blockade of a large conductance calcium-activated potassium channel in cultured rat hippocampal neurons." Thesis, 1992. http://hdl.handle.net/2429/3226.
Full text"The role of calcium ions in tumor necrosis factor-α-induced proliferation in C6 glioma cells." 2000. http://library.cuhk.edu.hk/record=b5895852.
Full textThesis submitted in: December 1999.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2000.
Includes bibliographical references (leaves 200-223).
Abstracts in English and Chinese.
Acknowledgements --- p.i
List of Abbreviations --- p.ii
Abstract --- p.v
撮要 --- p.viii
List of Tables --- p.x
List of Figures --- p.xi
Contents --- p.xv
Chapter CHAPTER 1 --- INTRODUCTION
Chapter 1.1 --- The General Characteristics of Glial Cells --- p.1
Chapter 1.1.1 --- Astrocytes --- p.1
Chapter 1.1.2 --- Oligodendrocytes --- p.5
Chapter 1.1.3 --- Microglial --- p.6
Chapter 1.2 --- Brain Injury and Astrocyte Proliferation --- p.6
Chapter 1.3 --- Reactive Astrogliosis and Glial Scar Formation --- p.9
Chapter 1.4 --- Astrocytes and Immune Response --- p.10
Chapter 1.5 --- Cytokines --- p.10
Chapter 1.5.1 --- Cytokines and the Central Nervous System (CNS) --- p.12
Chapter 1.5.2 --- Cytokines and brain injury --- p.13
Chapter 1.5.3 --- Cytokines-activated astrocytes in brain injury --- p.13
Chapter 1.5.4 --- Tumour Necrosis Factor-a --- p.14
Chapter 1.5.4.1 --- Types of TNF-α receptor and their sturctures --- p.16
Chapter 1.5.4.2 --- Binding to TNF-α --- p.17
Chapter 1.5.4.3 --- Different Roles of the TNF-a Receptor Subtypes --- p.17
Chapter 1.5.4.4 --- Role of TNF-α and Brain Injury --- p.19
Chapter 1.5.4.5 --- TNF-α Stimulates Proliferation of Astrocytes and C6 Glioma Cells --- p.23
Chapter 1.5.5 --- Interleukin-1 (IL-1) --- p.26
Chapter 1.5.5.1 --- Interleukin-1 and Brain Injury --- p.27
Chapter 1.5.6 --- Interleukin-6 (IL-6) --- p.28
Chapter 1.5.6.1 --- Interleukin-6 and brain injury --- p.29
Chapter 1.5.7 --- γ-Interferon (γ-IFN) --- p.30
Chapter 1.5.7.1 --- γ-Interferon and Brain Injury --- p.30
Chapter 1.6 --- Ion Channels and Astrocytes --- p.31
Chapter 1.6.1 --- Roles of Sodium Channels in Astrocytes --- p.33
Chapter 1.6.2 --- Role of Potassium Channels in Astrocytes --- p.33
Chapter 1.6.3 --- Importance of Calcium Ion Channels in Astrocytes --- p.34
Chapter 1.6.3.1 --- Function of Cellular and Nuclear Calcium --- p.34
Chapter 1.6.3.2 --- Nuclear Calcium in Cell Proliferation --- p.36
Chapter 1.6.3.3 --- Nuclear Calcium in Gene Transcription --- p.36
Chapter 1.6.3.4 --- Nuclear Calcium in Apoptosis --- p.38
Chapter 1.6.3.5 --- Spatial and Temporal Changes of Calcium-Calcium Oscillation --- p.39
Chapter 1.6.3.6 --- Calcium Signalling in Glial Cells --- p.39
Chapter 1.6.3.7 --- Calcium Channels in Astrocytes --- p.41
Chapter 1.6.3.8 --- Relationship Between [Ca2+]i and Brain Injury --- p.43
Chapter 1.6.3.9 --- TNF-α and Astrocyte [Ca2+]i --- p.45
Chapter 1.6.3.10 --- Calcium-Sensing Receptor (CaSR) --- p.46
Chapter 1.7 --- Protein Kinase C (PKC) Pathways --- p.49
Chapter 1.7.1 --- PKC and Brain Injury --- p.50
Chapter 1.7.2 --- Role of Protein Kinase C Activity in TNF-α Gene Expression in Astrocytes --- p.51
Chapter 1.7.3 --- PKC and Calcium in Astrocytes --- p.52
Chapter 1.8 --- Intermediate Early Gene (IEGs) --- p.54
Chapter 1.8.1 --- IEGs Expression and Brain Injury --- p.54
Chapter 1.8.2 --- IEGs Expression and Calcium --- p.55
Chapter 1.9 --- The Rat C6 Clioma Cells --- p.56
Chapter 1.10 --- The Aim of This Project --- p.58
Chapter CHAPTER 2 --- MATERIALS AND METHODS
Chapter 2.1 --- Materials --- p.61
Chapter 2.1.1 --- Sources of the Chemicals --- p.61
Chapter 2.1.2 --- Materials Preparation --- p.65
Chapter 2.1.2.1 --- Rat C6 Glioma Cell Line --- p.65
Chapter 2.1.2.2 --- C6 Glioma Cell Culture --- p.65
Chapter 2.1.2.2.1 --- Complete Dulbecco's Modified Eagle Medium (CDMEM) --- p.65
Chapter 2.1.2.2.2 --- Serum-free Dulbecco's Modified Eagle Medium --- p.66
Chapter 2.1.2.3 --- Phosphate Buffered Saline (PBS) --- p.66
Chapter 2.1.2.4 --- Recombinant Cytokines --- p.67
Chapter 2.1.2.5 --- Antibodies --- p.67
Chapter 2.1.2.5.1 --- Anti-TNF-Receptor 1 (TNF-R1) Antibody --- p.67
Chapter 2.1.2.5.2 --- Anti-TNF-Receptor 2 (TNF-R2) Antibody --- p.67
Chapter 2.1.2.6 --- Chemicals for Signal Transduction Study --- p.68
Chapter 2.1.2.6.1 --- Calcium Ionophore and Calcium Channel Blocker --- p.68
Chapter 2.1.2.6.2 --- Calcium-Inducing Agents --- p.68
Chapter 2.1.2.6.3 --- Modulators of Protein Kinase C (PKC) --- p.69
Chapter 2.1.2.7 --- Reagents for Cell Proliferation --- p.69
Chapter 2.1.2.8 --- Reagents for Calcium Level Measurement --- p.70
Chapter 2.1.2.9 --- Reagents for RNA Extraction and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) --- p.71
Chapter 2.1.2.10 --- Sense and Antisense Used --- p.72
Chapter 2.1.2.11 --- Reagents for Electrophoresis --- p.74
Chapter 2.2 --- Methods --- p.74
Chapter 2.2.1 --- Maintenance of the C6 Cell Line --- p.74
Chapter 2.2.2 --- Cell Preparation for Assays --- p.75
Chapter 2.2.3 --- Determination of Cell Proliferation --- p.76
Chapter 2.2.3.1 --- Determination of Cell Proliferation by [3H]- Thymidine Incorporation --- p.76
Chapter 2.2.3.2 --- Measurement of Cell Viability Using Neutral Red Assay --- p.77
Chapter 2.2.3.3 --- Measurement of Cell Proliferation by MTT Assay --- p.77
Chapter 2.2.3.4 --- Protein Assay --- p.78
Chapter 2.2.3.5 --- Data Analysis --- p.79
Chapter 2.2.3.5.1 --- The Measurement of Cell Proliferation by [3H]- Thymidine Incorporation --- p.79
Chapter 2.2.3.5.2 --- The Measurement of Cell growth in Neutral Red and MTT Assays --- p.79
Chapter 2.2.3.5.3 --- The Measurement of Cell Proliferationin Protein Assay --- p.79
Chapter 2.2.4 --- Determination of Intracellular Calcium Changes --- p.80
Chapter 2.2.4.1 --- Confocal Microscopy --- p.80
Chapter 2.2.4.1.1 --- Procedures for Detecting Cell Activity by CLSM --- p.81
Chapter 2.2.4.1.2 --- Precautions of CLSM --- p.82
Chapter 2.2.5 --- Determination of Gene Expression by Reverse- Transcription Polymerase Chain Reaction (RT-PCR) --- p.83
Chapter 2.2.5.1 --- RNA Preparation --- p.83
Chapter 2.2.5.1.1 --- RNA Extraction --- p.83
Chapter 2.2.5.1.2 --- Measurement of RNA Yield --- p.84
Chapter 2.2.5.2 --- Reverse Transcription (RT) --- p.84
Chapter 2.2.5.3 --- Polymerase Chain Reaction (PCR) --- p.85
Chapter 2.2.5.4 --- Separation of PCR Products by Agarose Gel Electrophoresis --- p.85
Chapter 2.2.5.5 --- Quantification of Band Density --- p.86
Chapter CHAPTER 3 --- RESULTS
Chapter 3.1 --- Effects of Different Drugs on C6 Cell Proliferation --- p.87
Chapter 3.1.1 --- Effects of Cytokines on C6 Cell Proliferation --- p.87
Chapter 3.1.1.1 --- Effect of TNF-α on C6 Proliferation --- p.88
Chapter 3.1.1.2 --- Effects of Other Cytokines on C6 Cell Proliferation --- p.92
Chapter 3.1.2 --- The Signalling Pathway of TNF-α induced C6 Cell Proliferation --- p.92
Chapter 3.1.2.1 --- The Involvement of Calcium Ions in TNF-α-induced C6Cell Proliferation --- p.95
Chapter 3.1.2.2 --- The Involvement of Protein Kinase C in TNF-α- induced C6 Cell Proliferation --- p.96
Chapter 3.1.3 --- Effects of Anti-TNF Receptor Subtype Antibodies on C6 Cell Proliferation --- p.102
Chapter 3.2 --- The Effect of in Tumour Necrosis Factor-α on Changesin Intracellular Calcium Concentration --- p.102
Chapter 3.2.1 --- Release of Intracellular Calcium in TNF-α-Treated C6 Cells --- p.104
Chapter 3.2.2 --- Effects of Calcium Ionophore and Calcium Channel Blocker on TNF-α-induced [Ca2+]i Release --- p.107
Chapter 3.2.3 --- Effects of Other Cytokines on the Change in [Ca2+]i --- p.109
Chapter 3.2.4 --- The Role of PKC in [Ca2+]i release in C6 Glioma Cells --- p.109
Chapter 3.2.4.1 --- Effects of PKC Activators and Inhibitors on the Changes in [Ca2+]i --- p.114
Chapter 3.3 --- Determination of Gene Expression by RT-PCR --- p.114
Chapter 3.3.1 --- Studies on TNF Receptors Gene Expression --- p.117
Chapter 3.3.1.1 --- Effect of TNF-α on TNF Receptors Expression --- p.117
Chapter 3.3.1.2 --- Effects of Other Cytokines on the TNF Receptors Expression --- p.119
Chapter 3.3.1.3 --- Effects of Anti-TNF Receptor Subtype Antibodies on the TNF-a-induced Receptors Expression --- p.121
Chapter 3.3.1.4 --- Effect of Calcium Ions on TNF Receptors Expression --- p.121
Chapter 3.3.1.4.1 --- Effect of Calcium Ionophore on TNF Receptors Expression --- p.126
Chapter 3.3.1.4.2 --- Effect of TNF-α Combination with A23187 on the Expression of TNF Receptors --- p.128
Chapter 3.3.1.4.3 --- Effects of Calcium Ionophore and Channel Blocker on TNF Receptors Expression --- p.130
Chapter 3.3.1.4.4 --- Effects of Calcium-Inducing Agents on TNF Receptors Gene Expressions --- p.130
Chapter 3.3.1.5 --- Effects of PKC Activator and Inhibitor on TNF-α- induced TNF Receptors Expressions --- p.135
Chapter 3.3.1.6 --- Effect of PKC and Ro31-8220 on IL-l-induced TNF Receptors Expressions --- p.138
Chapter 3.3.2 --- Expression of Calcium-sensing Receptor upon Different Drug Treatments --- p.138
Chapter 3.3.2.1 --- Effect of TNF-α on the Calcium-sensing Receptor Expression --- p.141
Chapter 3.3.2.2 --- Effects of Other Cytokines on CaSR Expression --- p.143
Chapter 3.3.2.3 --- Effect of A23187 on CaSR Expression --- p.143
Chapter 3.3.2.4 --- Effect of TNF-α and A23187 Combined Treatment on CaSR Expression --- p.146
Chapter 3.3.2.5 --- Effects of Calcium-inducing Agents on CaSR Expression --- p.149
Chapter 3.3.2.6 --- Effects of PKC Activator and PKC Inhibitor on CaSR Expression --- p.149
Chapter 3.3.3 --- Expression of PKC Isoforms upon Treatment with Different Drugs --- p.153
Chapter 3.3.3.1 --- Effect of TNF-α on the PKC Isoforms Expression --- p.155
Chapter 3.3.3.2 --- Effect of A23187 on the PKC Isoforms Expression --- p.155
Chapter 3.3.3.3 --- Effect of TNF-α and Calcium Ionophore Combined Treatment on PKC Isoforms Expression --- p.157
Chapter 3.3.3.4 --- Effects of Calcium-inducing Agents on PKC Isoforms Expression --- p.159
Chapter 3.3.4 --- Expression of the Transcription Factors c-fos and c-junin Drug Treatments --- p.161
Chapter 3.3.4.1 --- Effect of TNF-a on c-fos and c-jun Expression --- p.163
Chapter 3.3.4.2 --- Effect of A23187 on c-fos and c-jun Expression --- p.163
Chapter 3.3.4.3 --- Effect of TNF-a in Combination with A23187 on c- fos and c-jun Expression --- p.165
Chapter 3.3.4.4 --- Effects of Calcium-inducing Agents on c-fos and c- jun Expression --- p.167
Chapter 3.3.5 --- Effects of Different Drugs on Endogenous TNF-α Expression --- p.167
Chapter 3.3.5.1 --- Effect of TNF-α on Endogenous TNF-α Expression --- p.169
Chapter 3.3.5.2 --- Effect of A23187 on Endogenous TNF-α Expression --- p.169
Chapter 3.3.5.3 --- Effect of TNF-α in Combination with A23187 on the Expression of Endogenous TNF-α --- p.172
Chapter 3.3.5.4 --- Effects of Calcium-inducing Agents on Endogenous TNF-α Expression --- p.172
Chapter 3.3.6 --- Effect of Different Drugs on LL-1 Expression --- p.175
Chapter 3.3.6.1 --- Effect of TNF-a on IL-lα Expression --- p.177
Chapter 3.3.6.2 --- Effect of A23187 on the IL-lα Expression --- p.177
Chapter 3.3.6.3 --- Effect of Calcium Ionophore and TNF-α Combined Treatment on IL-1α Expression --- p.179
Chapter 3.3.6.4 --- Effects of Calcium-inducing Agents on IL-lα Expression --- p.179
Chapter 3.3.6.5 --- Effect of PKC Activator on the IL-1α Expression --- p.181
Chapter CHAPTER 4 --- DISCUSSIONS AND CONCLUSIONS
Chapter 4.1 --- "Effects of Cytokines, Ca2+ and PKC and Anti-TNF-α Antibodies on C6 Glioma Cells Proliferation" --- p.184
Chapter 4.2 --- The Role of Calcium in TNF-α-induced Signal Transduction Pathways --- p.186
Chapter 4.3 --- Gene Expressions in C6 Cells after TNF-a Stimulation --- p.187
Chapter 4.3.1 --- "Expression of TNF-α, TNF-Receptors and IL-1" --- p.187
Chapter 4.3.2 --- CaSR Expression --- p.190
Chapter 4.3.3 --- PKC Isoforms Expressions --- p.192
Chapter 4.3.4 --- Expression of c-fos and c-jun --- p.193
Chapter 4.4 --- Conclusion --- p.194
REFERENCES --- p.200
Longpré-Lauzon, Ariane. "Étude moléculaire des mécanismes d’action de potentiateurs du canal CFTR sur le canal KCa3.1." Thèse, 2009. http://hdl.handle.net/1866/4054.
Full textAirway epithelial cells are the site of Cl- secretion through CFTR. Cystic fibrosis is a fatal genetic disease caused by mutations in CFTR. The most frequent mutation in North America (∆F508) results in impaired maturation and altered channel gating of the protein. In the last years, several small molecules were identified by high throughput screening that could restore mutated CFTR function. Compounds addressing CFTR gating defects are referred to as potentiators. The basolateral K+ channel KCa3.1 has been documented to play a prominent role in establishing a suitable driving force for CFTR-mediated Clsecretion in airway epithelial cells. It has been shown, for example, that the application of 1-EBIO on T84 monolayers results in a sustained increase of Clsecretion and that this current can be reversed by application of CTX, a KCa3.1 inhibitor (Devor et al., 1996). Thus, in a global approach of transepithelial transport, the research for physiologically relevant CFTR potentiators should also consider their effects on the KCa3.1 channel. Electrophysiological patch clamp measurements and channel structural modification by site directed mutagenesis were used to characterize the action of CFTR potentiators on KCa3.1 and study their molecular mode of action. In this work we present results on the effects on KCa3.1 of several CFTR potentiators of different structures. We observed that the CFTR potentiators genistein, curcumin, SF-03 and VRT-532 could inhibit KCa3.1 activity at concentrations known to activate CFTR. Our results suggest that SF- 03 could act indirectly on KCa3.1 through a mechanism involving an accessory protein. Curcumin would also have an indirect inhibitory effect, probably mediated by the plasma membrane, as documented for other ion channels. A detailed study of VRT-532 revealed that this molecule has access to its binding site in a state independent manner, and is poorly effective on the V282G mutant of KCa3.1, which is constitutively active. These results suggest that VRT-532 could act through the CaM/KCa3.1 complex and require the presence of Ca2+ to inhibit channel activity. In contrast, CBIQ, another CFTR potentiator, succeeded to activate KCa3.1. Our results in single channel show that CBIQ vii destabilizes a non conducting state of the channel. We also showed that this molecule increases the apparent Ca2+ affinity as well as the channel open probability, even in saturating Ca2+ conditions. Experiences in which Ba2+ was used as a probe were also performed to determine if the action mechanism of CBIQ involves an effect on the selectivity filter. Our results showed that Ba2+ could displace CBIQ from its interacting site, suggesting that the increases in channel activity induced by CBIQ could result from a change in the energetics of the channel at the level of the selectivity filter. On the basis of our results, we conclude that CBIQ, a CFTR potentiator, could activate KCa3.1 by destabilizing a non conducting state of the channel, probably through an action near the selectivity filter region. Also, CFTR potentiators having an inhibitory effect on KCa3.1 are likely to act through the plasmic membrane, the CaM/KCa3.1 interaction or an accessory protein of the channel. In a perspective of future treatments for CF, our results indicate that CBIQ could be an efficient potentiator since this product stimulates KCa3.1 as well as CFTR. Conversly, the VRT-532 and SF-03 could be less efficient than on CFTR alone, due to their inhibition of KCa3.1.
Krishnan, Harish Ravikumar 1975. "Molecular and genetic mechanisms of ethanol tolerance in the fruit fly." Thesis, 2007. http://hdl.handle.net/2152/3727.
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