Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2008. / Vita. Includes bibliographical references.

Kai Hong Kwok. / Thesis submitted in: December 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 90-98). / Abstract also in Chinese. / Chapter Chapter 1 --- Introduction / Chapter 1.1. --- Classification of β-adrenoceptor in cardiovascular system --- p.1 / Chapter 1.2. --- Vasodilator effects of β-adrenoceptor-agonists and their mechanisms --- p.4 / Chapter 1.3. --- Role of endothelium in β-adrenoceptor-mediated vasodilation --- p.7 / Chapter 1.4. --- Role of K+ channels in β-adrenoceptor-mediated relaxation --- p.11 / Chapter 1.5. --- Other aspect regarding the vascular response to stimulation of B-adrenoceptor --- p.15 / Chapter 1.6. --- Clinical aspect of B-adrenoceptor agents --- p.15 / Chapter Chapter 2 --- Methods and Materials / Chapter 2.1. --- Tissue Preparation --- p.19 / Chapter 2.1.1. --- Preparation of the isolated rat mesenteric artery --- p.19 / Chapter 2.1.2. --- Removal of the functional endothelium --- p.19 / Chapter 2.1.3. --- Organ bath set-up --- p.20 / Chapter 2.1.4. --- Length-tension relationship and an optimal resting tension --- p.22 / Chapter 2.2. --- Experimental Procedure --- p.22 / Chapter 2.2.1. --- Relaxant effects of the B-adrenoceptor agonists --- p.24 / Chapter 2.2.2. --- Effects of putative K+ channel blockers --- p.24 / Chapter 2.2.3. --- Effects of inhibitors of nitric oxide activity --- p.25 / Chapter 2.2.4. --- Effect of indomethacin --- p.25 / Chapter 2.2.5. --- "Effects of K+ channel opener, nitric oxide donor and forskolin" --- p.26 / Chapter 2.3. --- Chemicals and Solutions --- p.26 / Chapter 2.3.1. --- Chemicals and drugs --- p.26 / Chapter 2.3.2. --- Preparation of drug stock solutions --- p.26 / Chapter 2.3.3. --- Solutions --- p.28 / Chapter 2.4. --- Statistical Analysis --- p.28 / Chapter Chapter 3 --- Results / Chapter 3.1. --- Relaxant Effect of Isoprenaline --- p.29 / Chapter 3.1.1. --- Relaxant effect of isoprenaline --- p.29 / Chapter 3.1.2. --- Effects of inhibitors of nitric oxide activity --- p.29 / Chapter 3.1.3. --- Effect of charybdotoxin on the vasorelaxant response to isoprenaline --- p.32 / Chapter 3.1.4. --- Effect of glibenclamide on the vasorelaxant response to isoprenaline --- p.32 / Chapter 3.1.5. --- Effect of TPA+ on isoprenaline-induced relaxation --- p.36 / Chapter 3.1.6. --- Effect of TPA+ in the presence of iberiotoxin or glibenclamide --- p.36 / Chapter 3.1.7. --- Effect of Ba2+ on the vasorelaxant effect of isoprenaline --- p.41 / Chapter 3.1.8. --- Effect of raising extracellular K+ on isoprenaline-mediated relaxation --- p.41 / Chapter 3.2. --- Relaxant Effect of Dobutamine --- p.44 / Chapter 3.2.1. --- Effects of inhibitors of endothelium-derived factors on the relaxant effect of dobutamine --- p.44 / Chapter 3.2.2. --- Antagonism of the effect of dobutamine by β1-adrenoceptor antagonist --- p.44 / Chapter 3.2.3. --- Effects of putative Kca channel blockers on the relaxant effect of dobutamine --- p.51 / Chapter 3.2.4. --- Effect of TPA+ on the relaxant effect of dobutamine --- p.55 / Chapter 3.2.5. --- Effect of raising extracellular K+ on the relaxant effect of dobutamine --- p.55 / Chapter 3.3. --- Relaxant Effect of Fenoterol --- p.57 / Chapter 3.3.1. --- Effect of inhibitors of nitric oxide activity on the relaxant effect of fenoterol --- p.57 / Chapter 3.3.2. --- Effect of charybdotoxin on the relaxant effect of fenoterol --- p.57 / Chapter 3.3.3. --- Effect of TPA+ on the relaxant effect of fenoterol --- p.64 / Chapter 3.3.4. --- Effect of glibenclamide on the relaxant effect of fenoterol --- p.64 / Chapter 3.3.5. --- Effect of raising extracellular K+ on fenoterol-mediated relaxation --- p.64 / Chapter 3.4. --- Effects of cAMP- and cGMP-elevating agents --- p.69 / Chapter 3.4.1. --- Effects of inhibitors of endothelium-derived factors on the relaxation induced by nitroprusside and forskolin --- p.69 / Chapter 3.4.2 --- Effect of charybdotoxin on relaxant effect of forskolin --- p.69 / Chapter 3.4.3 --- Effect of Ba2+ on the vasorelaxant effect of forskolin --- p.76 / Chapter 3.4.4 --- Effect of TPA+ on the relaxant effect of forskolin --- p.76 / Chapter 3.4.5 --- Effect of glibenclamide on the relaxant effects of forskolin and cromakalim --- p.76 / Chapter Chapter 4 --- Discussion / Chapter 4.1. --- Effect of Isoprenaline and Fenoterol --- p.77 / Chapter 4.2. --- Effect of Dobutamine --- p.83 / Chapter 4.3. --- Conclusion --- p.88 / References --- p.90 / Publications --- p.98

This thesis records a series of experiments conducted to gain further insight into factors which influence the expression, ligand binding and functional activity of the beta-2 adrenergic receptor. These studies were prompted by previous reports that the postulated beta-2 adrenergic receptor abnormality in allergic asthma could be induced, induced by autoantibodies. I established and optimised beta-2 adrenergic receptor ligand binding and functional assays in guinea pig lung membranes and then conducted an original study of beta adrenergic receptor expression in the guinea pig foetal lung. I found that beta adrenergic receptor expression in the foetal lung was dormant for 80% of the gestation period. After day 53 there was a surge in receptor expression which increased beyond term.

G protein coupled receptors, G proteins and their downstream effectors adenylyl cyclase (ACs) were thought to transiently interact at the plasma membrane by random collisions following agonist stimulation. However a growing number of studies have suggested that a major revision of this paradigm was necessary to account for signal transduction specificity and efficiency. The revised model suggests that signalling proteins are pre-assembled as stable macromolecular complexes together with modulators of their activity prior to receptor activation. How and where these signalling complexes form and the mechanisms governing their assembly and maintenance are not completely understood yet. Initially, we addressed this question by exploring AC2 interaction with beta2-adrenergic receptors (beta2ARs) and heterotrimeric G proteins as parts of a pre-assembled signalling complex. Using a combination of biophysical and biochemical techniques, we showed that AC2 interacts with them before it is trafficked to the cell surface in transfected HEK-293 cells. These interactions are constitutive and do not require stimulation by receptor agonists. Furthermore, the use of dominant-negative Rab/Sar monomeric GTPases and dominant-negative heterotrimeric G protein subunits proved that AC2/beta2AR and AC2/Gbetagamma interactions occurred in the ER as measured using both BRET and co-immunoprecipitation experiments, while interaction of the Galpha subunits with the above complexes occurred at a slightly later stage. Both Galpha and Gbetagamma played a role in stabilizing these complexes. Our data also demonstrated that stimulation of AC was still possible when the complex remained on the inside of the cell but was reduced when the GalphaS/AC2 interaction was blocked, suggesting that the addition of the GalphaS subunit was required to render the nascent complexes functional prior to trafficking to proper sites of action. Next, we tackled the issue of higher order assembly of effectors and G proteins, using two different AC isoforms and GalphaS as a model. We demonstrated that AC2 can form heterodimers with AC5 through direct molecular interaction in unstimulated HEK-293 cells. AC2/5 heterodimerization resulted in a reduced total level of AC2 expression, which affected cellular accumulation of cAMP upon forskolin stimulation. The AC2/5 complex was stable in presence of receptor or forskolin stimulation. We provided evidence that co-expression with GalphaS increased the affinity of AC2 for AC5 as monitored by BRET. In particular, the complex formed by AC2/5 lead to synergistic accumulation of cAMP in presence of GalphaS and forskolin, with respect to either of the parent AC isoforms themselves. Finally, we also showed that this complex can be detected in native tissues, as AC2 and AC5 could be co-immunoprecipiated from lysates of mouse heart. Taken together, we provided evidence for stable formation of signalling complexes involving receptor/G proteins/adenylyl cyclase or G proteins/heterodimeric adenylyl cyclases and that G proteins play a crucial role for their assembly and function.

Thesis (doctoral)--Umeå Universitet, Sweden, 1991. / Extra t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Umeå Universitet, Sweden, 1991. / Extra t.p. with thesis statement inserted. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

No description available.

Yes / The Sphingosine-1-phosphate receptor 1 (S1PR1) and β1-adrenergic receptor (β1AR) are G protein-coupled receptors (GPCRs) expressed in the heart. These two GPCRs have opposing actions on adenylyl cyclase due to differential G protein-coupling. Importantly, both of these receptors can be regulated by the actions of GPCR kinase-2 (GRK2), which triggers desensitization and down-regulation processes. Although, classical signaling paradigms suggest that simultaneous activation of β1ARs and S1PR1s in a myocyte would simply be opposing action on cAMP production, in this report we have uncovered a direct interaction between these two receptors with a regulatory involvement of GRK2. In HEK293 cells overexpressing both β1AR and S1PR1, we demonstrate that β1AR down-regulation can occur after sphingosine 1-phosphate (S1PR1 agonist) stimulation while S1PR1 down-regulation can be triggered by isoproterenol (βAR agonist) treatment. This cross-talk between these two distinct GPCRs appears to have physiological significance since they interact and show reciprocal regulation in mouse hearts undergoing chronic βAR stimulation and also in a rat model of post-ischemic heart failure (HF). We demonstrate that restoring cardiac plasma membrane levels of S1PR1 produce beneficial effects counterbalancing deleterious β1AR overstimulation in HF.

Le diabète prédispose à des complications affectant divers organes comme le systémecardiovasculaire. La cardiopathie ischémique chez les patients diabétiques pourrait être liée àl'accumulation de produits avancés de glycation (AGEs). Dans les coeurs de rats ischémiques,l'expression des récepteurs aux AGEs et de ses ligands est considérablement augmentée etimpliquée dans les lésions de l'ischémie / reperfusion (I / R), même en absence de diabète. Ila été récemment rapporté que le myocarde humain diabétique ne peut pas être protégé par lepréconditionnement. Dans ce contexte, notre hypothèse était que le préconditionnement β1-adrénergique pourrait être modifié en présence d'AGE. En utilisant un modèle de coeur isolénon travaillant de rat, cette étude a pour but d’étudier les effets des AGEs sur lacardioprotection induite par la stimulation des récepteurs β1-adrénergiques (β1-ARs) par lexamotérol (xa). Les effets bénéfiques induits par le xa pendant la reperfusion ont étésupprimés par l'administration de l’albumine glyquée (Alb-Gly) pendant la perfusion du xa,tandis que l’albumine (Alb) n’a pas modifié cette protection. Ces résultats suggèrent que lesAGEs suppriment la cardioprotection résultant de l'activation de la voie β1-AR ce quicontribue à des dommages cardio-vasculaires chez les patients diabétiques.D’ autre part, le pyridoxal 5’-phosphate (PLP), un métabolite naturel de la pyridoxine qui estun antagoniste des récepteurs purinergiques, empêche la surcharge cellulaire en calcium etpeut réduire les dommages d'ischémie-reperfusion. Plusieurs travaux ont mis en evidence unediminution des taux du PLP chez les patients souffrant d'un infarctus du myocarde par rapportà un groupe témoin sain. Plus récemment, il a été signalé qu’un taux bas de PLP confère unrisque indépendant de maladie coronaire. Cette corrélation de la réduction du PLP chez lespatients souffrant d’infarctus est soutenue par les effets préventifs de la vitamine B6 sur lesmaladies coronaires et le diabète. Plusieurs travaux ont montré que le PLP et la pyridoxaminepréviennent la progression de la néphropathie induite par la STZ chez les rats diabétiques eninhibant la formation des AGEs. En utilisant un modèle de coeur isolé non-travaillant de rat,cette étude a examiné les mécanismes de préconditionnement pharmacologique (PC) induitpar la stimulation des récepteurs P2Y par le pyridoxal-5'-phosphate (PLP). La suppression del'effet cardioprotecteur du PLP par le MRS2578, antagoniste des récepteurs P2Y6 et parl’U73122 qui bloque la phospholipase C est en accord avec l’implication du récepteur P2Y6dans le préconditionnement. La suppression de l'effet cardioprotecteur du PLP par l'AMPαS,antagoniste des récepteurs P2Y11, l’H89 inhibiteur de la PKA et par l’U73122 démontrel’implication aussi des récepteurs P2Y11 dans ce préconditionnement. L’exposition préischémique à des concentrations nanomolaires de PLP protège contre les lésions de l’ I / R.P2Y11 et P2Y6 représentent ainsi les récepteurs candidats les plus probables pour le PCcardiaque induit par le PLP. / Diabetes predisposes to complications affecting various organs such as cardiovascular system.Ischemic heart disease in diabetic patients might be linked to the accumulation ofadvanced-glycation end products (AGEs). In ischemic rat hearts, expression of receptor forAGEs and its ligands is significantly enhanced and involved in cardiac ischemia/reperfusion(I/R) injury even in the absence of diabetes. It has recently been reported that diabetic humanmyocardium cannot be protected by preconditioning. In this context, our hypothesis was thatβ1-adrenergic preconditioning might be altered in the presence of AGEs. Using an isolatednon-working rat heart model, this study investigated the effect of AGEs on cardioprotectioninduced by transient β1-adrenoceptor (β1-AR) stimulation with xamoterol (xa). The beneficialeffects induced by xa during reperfusion were suppressed by the administration of glycatedalbumin (Gly-Alb) during xa infusion, whereas albumin (Alb) did not hamper xa inducedprotection. These results suggest that AGEs suppress the cardioprotection resulting from theactivation of β1-ARs and thus might contribute to cardiovascular damages seen in diabeticpatients.Pyridoxal 5'-phosphate (PLP), a natural metabolite of pyridoxine which is an antagonist ofpurinergic receptors prevents cellular calcium overload and may reduce ischemia-reperfusioninjury. Low plasma pyridoxal-5′-phosphate levels have been observed in patients sufferingfrom myocardial infarction, when compared with a healthy control group. More recently, lowPLP level has been reported to confer an independent risk for coronary artery disease. Thefact that this correlation of PLP reduction in infarct patients has functional importance issupported by the preventive effects of vitamin B6 on coronary heart disease and diabetes. PLPprevented progression of nephropathy in STZ-induced diabetic rats by inhibiting formation ofAGEs. Using an isolated non-working rat heart model, this study investigated the mechanismsof pharmacological pre-conditioning (PC) induced by P2Y receptor stimulation withpyridoxal-5’-phosphate (PLP). The suppression of the cardioprotective effects of PLP byMRS2578 and U73122 is in agreement with the P2Y6 receptor as a receptor for PLP-inducedPC.The suppression of the cardioprotective effects of PLP by AMPαS, the PKA inhibitor (H89),and (U73122) is in agreement with the P2Y11 receptor as a receptor for PLP-induced PC.Pre-ischemic exposure to nanomolar concentrations of PLP is protective against I/R. P2Y11and P2Y6 represent the most likely candidate receptors for PLP-induced cardiac PC.

by Shan Sze Wan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 145-166). / Abstracts in English and Chinese. / Title --- p.i / Abstract --- p.ii / 摘要 --- p.v / Acknowledgements --- p.vii / Table of Contents --- p.viii / List of Abbreviations --- p.xiv / List of Figures --- p.xvii / List of Tables --- p.xx / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- What are the general functions of cytokines? --- p.2 / Chapter 1.2 --- What is TNP-α? --- p.4 / Chapter 1.3 --- Actions of TNF-α --- p.5 / Chapter 1.4 --- General functions of TNF-α in astrocytes --- p.6 / Chapter 1.5 --- TNF-α receptors (TNF-Rs) --- p.8 / Chapter 1.6 --- Second messengers induced by TNP-α --- p.10 / Chapter 1.7 --- Glial Cells --- p.11 / Chapter 1.7.1 --- Oligodendroglia --- p.12 / Chapter 1.7.2 --- Brain Macrophages (Microglia) --- p.12 / Chapter 1.7.3 --- Astrocytes --- p.14 / Chapter 1.7.3.1 --- Functions of astrocytes --- p.15 / Chapter 1.8 --- "Brain injury, astrogliosis and scar formation" --- p.20 / Chapter 1.9 --- β-Adrenergic receptors (β-ARs) --- p.21 / Chapter 1.9.1 --- The active functional unit: the receptor complex --- p.22 / Chapter 1.9.2 --- General functions and distribution of β-ARs --- p.22 / Chapter 1.10 --- Functions of β-ARs in astrocytes --- p.24 / Chapter 1.10.1 --- Regulations of astrogliosis by β-ARs --- p.24 / Chapter 1.10.1.1 --- β-ARs are expressed in normal optic nerves and up-regulated after nerve crush --- p.24 / Chapter 1.10.1.2 --- Injury-induced alterations in endogenous catecholamine leads to enhanced β-AR activation --- p.25 / Chapter 1.10.1.3 --- β-AR blockade suppresses glial scar formation --- p.25 / Chapter 1.10.1.4 --- β-AR agonists affect the proliferation of astrocytes in normal brain --- p.26 / Chapter 1.11 --- Manganese Superoxide Dismutase (MnSOD) --- p.27 / Chapter 1.11.1 --- MnSOD is the target gene of NF-kB --- p.29 / Chapter 1.11.2 --- Induction of MnSOD by proinflammatory cytokines in rat primary astrocytes --- p.29 / Chapter 1.11.3 --- SMase and ceramides induce MnSOD in various cell types --- p.30 / Chapter 1.12 --- Why do we use C6 glioma cells? --- p.31 / Chapter 1.13 --- Aims and Scopes of this project --- p.32 / Chapter Chapter 2 --- MATERIALS AND METHODS / Chapter 2.1 --- Materials --- p.36 / Chapter 2.1.1 --- Cell Line --- p.36 / Chapter 2.1.2 --- Cell Culture Reagents --- p.36 / Chapter 2.1.2.1 --- Complete Dulbecco´ةs modified Eagle medium (CDMEM) --- p.36 / Chapter 2.1.2.2 --- Rosewell Park Memorial Institute (RPMI) medium --- p.37 / Chapter 2.1.2.3 --- Phosphate buffered saline (PBS) --- p.37 / Chapter 2.1.3 --- Recombinant cytokines --- p.38 / Chapter 2.1.4 --- Chemicals for signal transduction study --- p.38 / Chapter 2.1.4.1 --- Modulators of protein kinase C (PKC) --- p.38 / Chapter 2.1.4.2 --- Modulator of protein kinase A (PKA) --- p.39 / Chapter 2.1.4.3 --- β-Adrenergic agonist and antagonist --- p.39 / Chapter 2.1.5 --- Antibodies --- p.40 / Chapter 2.1.5.1 --- Anti-TNF-receptor type 1 (TNF-R1) antibody --- p.40 / Chapter 2.1.5.2 --- Anti-TNF-receptor type 2 (TNF-R2) antibody --- p.41 / Chapter 2.1.5.3 --- Anti-βi-adrenergic receptor (βl-AR) antibody --- p.42 / Chapter 2.1.5.4 --- Anti-β2-adrenergic receptor (β2-AR) antibody --- p.42 / Chapter 2.1.5.5 --- Antibody conjugates --- p.43 / Chapter 2.1.6 --- Reagents for RNA isolation --- p.43 / Chapter 2.1.7 --- Reagents for reverse transcription-polymerase chain reaction (RT-PCR) --- p.43 / Chapter 2.1.8 --- Reagents for electrophoresis --- p.45 / Chapter 2.1.9 --- Reagents and buffers for Western blot --- p.45 / Chapter 2.1.10 --- Other chemicals and reagents --- p.47 / Chapter 2.2 --- Maintenance of rat C6 glioma cell line --- p.47 / Chapter 2.3 --- RNA isolation --- p.48 / Chapter 2.3.1 --- Measurement of RNA yield --- p.49 / Chapter 2.4 --- Reverse transcription-polymerase chain reaction (RT-PCR) --- p.50 / Chapter 2.5 --- Western blot analysis --- p.52 / Chapter Chapter 3 --- RESULTS / Chapter 3.1 --- Effect of TNF-α on the expression of TNF-receptors (TNFRs) in C6 glioma cells --- p.55 / Chapter 3.1.1 --- Effect of TNF-α on TNF-R1 and -R2 mRNA expression in C6 cells --- p.56 / Chapter 3.1.2 --- The signaling systems mediating TNP-α-induced TNF-R2 expression in C6 cells --- p.57 / Chapter 3.1.2.1 --- The involvement of PKC in TNF-α-induced TNF-R2 expression in C6 cells --- p.57 / Chapter 3.1.2.2 --- Effect of PMA on the TNF-R protein levels in C6 cells --- p.63 / Chapter 3.1.2.3 --- Effect of Ro31 on the TNF-α-induced TNF-R protein level in C6 cells --- p.65 / Chapter 3.1.2.4 --- Effect of PKA activator on the level of TNF-R2 mRNA in C6 cells --- p.67 / Chapter 3.2 --- Effect of TNP-α on the expression of β1- and β2-adrenergic receptors (β1- and β2-ARs) in C6 glioma cells --- p.69 / Chapter 3.2.1 --- Effect of TNF-α on β1- and β2-ARs mRNA expression in C6 cells --- p.70 / Chapter 3.2.2 --- The signaling systems mediating TNF-α-induced β1- and β2-AR expression in C6 cells --- p.70 / Chapter 3.2.2.1 --- The involvement of PKC mechanism between TNF-α and β-ARs in C6 cells --- p.71 / Chapter 3.2.2.2 --- Effect of PMA on the β1- and β2-ARs protein level in C6 cells --- p.76 / Chapter 3.2.2.3 --- Effect of Ro31 on the TNF-α-induced β1- and β2-AR protein levels in C6 cells --- p.78 / Chapter 3.2.2.4 --- Effect of dbcAMP on the levels of βl- and β2-ARs mRNA in C6 cells --- p.80 / Chapter 3.3 --- Relationship between TN1F-R2 and β-adrenergic mechanism in C6 cells --- p.82 / Chapter 3.3.1 --- Effects of isproterenol and propranolol on endogenous TNF-α mRNA levels in C6 cells --- p.82 / Chapter 3.3.2 --- Effects of isoproterenol and propranolol on TNF-R2 mRNA levels in C6 cells --- p.83 / Chapter 3.3.3 --- Effects of β1-agonist and antagonist on endogenous TNF-α mRNA expression in C6 cells --- p.87 / Chapter 3.3.4 --- Effects of β1-agonist and antagonist on TNF-R2 mRNA expression in C6 cells --- p.91 / Chapter 3.3.5 --- Effects of β2-agonist and antagonist on endogenous TNF-α mRNA in C6 cells --- p.93 / Chapter 3.3.6 --- Effects of β2-agonist and antagonist on TNF-R2 mRNA in C6 cells --- p.100 / Chapter 3.4 --- Effect ofTNF-α on the expression of a transcriptional factor nuclear factor kappa B (NF-kB) in C6 glioma cells --- p.102 / Chapter 3.4.1 --- Effect ofTNF-α on NF-kB (p50) mRNA expression in C6 cells --- p.106 / Chapter 3.4.2 --- Effect of β-agonist and antagonist on NF-kB (p50) mRNA expression in C6 cells --- p.108 / Chapter 3.4.3 --- Effect of PMA and Ro31 on the levels of NF-kB mRNA in C6 cells --- p.109 / Chapter 3.5 --- Effects of TNF-α on the expression of manganese superoxide dismutase (MnSOD) in C6 glioma cells --- p.111 / Chapter 3.5.1 --- Effects of TNF-α on MnSOD and Cu-ZnSOD mRNAs expression in C6 cells --- p.114 / Chapter 3.5.2 --- Effects of β-agonist and β-antagonist on MnSOD mRNA expression in C6 cells --- p.115 / Chapter 3.5.3 --- Effects of PKC activator and inhibitor on the levels of MnSOD mRNA in C6 cells --- p.117 / Chapter Chapter 4 --- DISCUSSION AND CONCLUSION / Chapter 4.1 --- Effects of TNF-α on the expression of TNF-receptors (TNFRs) in C6 glioma cells --- p.122 / Chapter 4.2 --- Effects of TNF-a on the expression of β1- and β2-adrenergic receptors (β1 and β2-ARs) in C6 glioma cells --- p.126 / Chapter 4.3 --- Relationship between TNF-α and β-adrenergic mechanism in C6 cells --- p.128 / Chapter 4.4 --- Effects of TNF-α on the expression of a transcriptional factor nuclear factor kappa B (NF-kB) in C6 glioma cells --- p.131 / Chapter 4.5 --- Effects of TNF-α on the expression of manganese superoxide dismutase (MnSOD) in C6 glioma cells --- p.133 / Chapter 4.6 --- Possible sources of β-agonists --- p.136 / Chapter 4.7 --- Conclusions --- p.137 / Appendix A --- p.143 / References --- p.145