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Articles 121 - 150 of 308
Full-Text Articles in Physiology
Endocannabinoid Biosynthetic Enzyme Mrna: Patterns Of Expression In Hippocampus And Ventral Tegmental Area And Effects On Synaptic Plasticity, Collin Brutch Merrill
Endocannabinoid Biosynthetic Enzyme Mrna: Patterns Of Expression In Hippocampus And Ventral Tegmental Area And Effects On Synaptic Plasticity, Collin Brutch Merrill
Theses and Dissertations
Endocannabinoids (eCBs) are lipophilic signals that are produced by postsynaptic neurons in an activity-dependent manner, and signal in a retrograde fashion to modulate neurotransmitter release. As such, eCBs are highly involved in synaptic plasticity, a process that strengthens or weakens synapses. eCB-mediated synaptic plasticity is involved in many brain processes including learning, short-term memory, and adaptive reward, which are processed in the hippocampus and ventral tegmental area (VTA), respectively. However, the expression of eCB biosynthetic enzyme mRNA within hippocampal and VTA neurons, as well as the relationship between these mRNA species and the occurrence of synaptic plasticity, remains unclear. The …
Inhibition Of Pim And Axl Kinases As Potential Treatments For A Variety Of Hematological Malignancies And Solid Tumors, Kent James Carpenter
Inhibition Of Pim And Axl Kinases As Potential Treatments For A Variety Of Hematological Malignancies And Solid Tumors, Kent James Carpenter
Theses and Dissertations
This thesis is divided into three chapters. In each case, the goal is to achieve inhibition of a growth kinase (PIM or AXL) and subsequent arrest of cell growth and induction of apoptosis (in vitro cell culture models) or decrease in tumor volume (in vivo xenograft studies). Chapter one and chapter two discuss inhibition of proviral integration site for Moloneymurine leukemia virus (PIM) kinases. The three PIM kinases, PIM-1, PIM-2, and PIM-3, are a subfamily of serine/threonine kinases that are known to be involved in signaling pathways as downstream effectors of signal transducer and activator of transcription-5 (STAT5) signaling and …
Evaluation Of The Physiological Effects Of Reduced Hydroxocobalamin On Acute Carbon Monoxide Toxicity, Alden Newcomb
Evaluation Of The Physiological Effects Of Reduced Hydroxocobalamin On Acute Carbon Monoxide Toxicity, Alden Newcomb
Theses and Dissertations
Carbon monoxide (CO) poisoning represents a global health threat responsible for hundreds of thousands of hospital visits and tens of thousands of deaths annually. Oxygen therapy is the only current approved treatment for CO poisoning. Previous work published in the 1970’s and research conducted in the VCURES lab group has indicated that a reduced form of vitamin B12, hydroxocobalamin (B12r), can potentially serve as an antidote for CO poisoning by converting CO bound to hemoglobin to carbon dioxide (CO2) and mitigating the deleterious neurological effects of CO poisoning. For the first time in documented literature we successfully used a Clark-type …
Biochemical And Structural Studies Of Aav-2 Rep68-Aavs1 Complex Assembly, Clayton Bishop
Biochemical And Structural Studies Of Aav-2 Rep68-Aavs1 Complex Assembly, Clayton Bishop
Theses and Dissertations
Multiple DNA transactions are at the center of almost all processes regulating the AAV life cycle. A common feature shared by all transactions is the binding of the large AAV Rep proteins Rep78/Rep68 onto DNA sites harboring multiple GCTC repeats. AAV mediated site-specific integration is contingent upon the formation of a productive complex between Rep78/Rep68 and the AAVS1 site located at chromosome 19. In order to understand the mechanistic details of the initial assembly process we carried out equilibrium binding experiments of Rep68 and its individual domains with a 42-mer AAVS1 site. Results show that although Rep68 binds AAVS1 with …
Characterization Of The Biological Role Of A Putative Porphyromonas Gingivalis Rna-Binding Protein, Ramana Cvitkovic
Characterization Of The Biological Role Of A Putative Porphyromonas Gingivalis Rna-Binding Protein, Ramana Cvitkovic
Theses and Dissertations
Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is a major etiological agent in the initiation and progression of severe forms of periodontal disease. Oral bacteria like P. gingivalis are subject to continually changing conditions as a consequence of host eating, oral hygiene patterns and subgingival temperatures. As such survival requires an adaptive response to environmental cues, but little is known about the mechanism by which P. gingivalis controls co- and post-transcriptional regulation of RNA levels and potentially protein expression. RNA-binding proteins (RBPs) are evolutionarily conserved across species and are involved in such regulatory mechanisms. However, P. gingivalis currently has no identified …
Comparison Of Two Different Sprint Interval Training Work-To-Rest Ratios On Acute Metabolic And Inflammatory Responses, Christopher R. Harnish
Comparison Of Two Different Sprint Interval Training Work-To-Rest Ratios On Acute Metabolic And Inflammatory Responses, Christopher R. Harnish
Theses and Dissertations
High intensity exercise is believed to yield greater results on health and human performance than moderate intensity exercise. Extensive research indicates that not only do high-intensity interval training (HIT) and sprint interval training (SIT) produce significant improvements in cardiovascular fitness and disease, they may be more effective at improving long-term metabolic function, including insulin sensitivity (Si), by producing more mitochondria. Moreover, compliance rates for HIT and SIT participation are reported to be the same or better than traditional moderate intensity exercise. Because lack of time is often cited as major hindrance to exercise participation, SIT is also seen as a …
Regulation Of Pancreatic Α And Β Cell Function By The Bile Acid Receptor Tgr5, Divya Prasanna Kumar
Regulation Of Pancreatic Α And Β Cell Function By The Bile Acid Receptor Tgr5, Divya Prasanna Kumar
Theses and Dissertations
The discovery that bile acids act as endogenous ligands of the membrane receptor TGR5 and the nuclear receptor FXR increased their significance as regulators of cholesterol, glucose and energy metabolism. Activation of TGR5, expressed on enteroendocrine L cells, by bile acids caused secretion of GLP-1, which stimulates insulin secretion from pancreatic β cells. Expression of TGR5 on pancreatic islet cells and the direct effect of bile acids on the endocrine functions of pancreas, however, are not fully understood. The aim of this study was to identify expression of TGR5 in pancreatic islet cells and determine the effect of bile acids …
Involvement Of Ampk And Ap-1 Biochemical Pathways In Il-6 Regulation Of Steroidogenic Enzymes In The Adrenal Cortex, Matharage Shenali De Silva
Involvement Of Ampk And Ap-1 Biochemical Pathways In Il-6 Regulation Of Steroidogenic Enzymes In The Adrenal Cortex, Matharage Shenali De Silva
Theses and Dissertations
The adrenal cortex is a crucial endocrine gland in the mammalian stress response. In chronic inflammatory stress, cortisol is elevated whereas adrenal androgens are decreased. Furthermore, ACTH levels have poor correlation with the plasma cortisol in these conditions, thus suggesting that other factors are driving the stress response during chronic inflammatory stress. Interleukin-6 (IL-6), a cytokine which is released during chronic inflammatory stress, is assumed to be one such factor. Thus the biochemical pathways by which IL-6 increases cortisol release from the zona fasciculata (ZF), and decreases adrenal androgen release from the zona reticularis (ZR) were investigated. Since IL-6 activates …
Fgf4 Induced Wnt5a Gradient In The Limb Bud Mediates Mesenchymal Cell Directed Migration And Division, John C. Allen
Fgf4 Induced Wnt5a Gradient In The Limb Bud Mediates Mesenchymal Cell Directed Migration And Division, John C. Allen
Theses and Dissertations
The AER has a vital role in directing embryonic limb development. Several models have been developed that attempt to explain how the AER directs limb development, but none of them are fully supported by existing data. I provide evidence that FGFs secreted from the AER induce a gradient of Wnt5a. I also demonstrate that limb mesenchyme grows toward increasing concentrations of Wnt5a. We hypothesize that the changing shape of the AER is critical for patterning the limb along the proximal to distal axis. To better understand the pathway through which Wnt5a elicits its effects, we have performed various genetic studies. …
Endocannabinoid-Dependent Long-Term Depression Of Ventral Tegmental Area Gaba Neurons, Jared Mark Weed
Endocannabinoid-Dependent Long-Term Depression Of Ventral Tegmental Area Gaba Neurons, Jared Mark Weed
Theses and Dissertations
GABA neurons in the ventral tegmental area of the midbrain are important components in the brain's reward circuit. Long term changes in this circuit occur through the process of synaptic plasticity. It has been shown that high frequency stimulation, as well as treatment with endocannabinoids, can cause GABA neurons in the ventral tegmental area to undergo long term depression, a form of synaptic plasticity that decreases excitability of cells. The present study elaborates on the mechanism whereby high frequency stimulation can result in long term depression of ventral tegmental area GABA neurons. Using the whole cell patch clamp technique in …
Differential Effects Of Short-Chain Fatty Acids On Motility Of Guinea Pig Proximal And Distal Colon, Norman Hurst
Differential Effects Of Short-Chain Fatty Acids On Motility Of Guinea Pig Proximal And Distal Colon, Norman Hurst
Theses and Dissertations
NTRODUCTION: Colonic bacteria produce short-chain fatty acids (SCFAs) by fermentation of dietary carbohydrates and fiber. The production of SCFAs is greatest in proximal colon where propulsion is likely to be highly dependent on chemical/nutrient stimuli. Unabsorbed SCFAs entering the distal colon are likely to modify peristalsis initiated by fecal pellet-induced distension. AIM: To determine the effect of individual SCFAs on propulsive contractions in guinea pig proximal colon and on pellet propulsion in distal colon. METHODS: Proximal colon was excised, cannulated and placed in Krebs buffer in an organ bath. After equilibration, the colon was distended with 1ml of Krebs buffer …
Effects Of Nitrite And Oxygen On Angiogenesis In Vascular Networks Of The Chicken Embryo, Michael Connery
Effects Of Nitrite And Oxygen On Angiogenesis In Vascular Networks Of The Chicken Embryo, Michael Connery
Theses and Dissertations
Nitric oxide (NO) is an important mediator of angiogenesis and is primarily produced endogenously through the action of nitric oxide synthase (NOS). An alternate pathway for NO production is the conversion of nitrite to NO, which depends on the presence of hemoglobin (Hb) and hypoxic conditions. The angiogenic effects of topically applied sodium nitrite on two vascular beds in the ex ovo chicken embryonic model of angiogenesis were assessed. Gas barrier films were used to modulate local oxygen levels in the chorioallantoic membrane (CAM), a respiratory vascular network, and the area vasculosa (AV) on the yolk sac, a typical peripheral …
Protein Kinase C Dependent Inhibition Of Kir3.2 (Girk2) Channel Activity And Its Molecular Determinants, Scott Adney
Protein Kinase C Dependent Inhibition Of Kir3.2 (Girk2) Channel Activity And Its Molecular Determinants, Scott Adney
Theses and Dissertations
Inwardly rectifying potassium (Kir) channels are critically important for regulating resting membrane potential in excitable cells, a job underscored by the severe pathophysiology associated with channel dysfunction. While all Kir channels require the activating lipid PIP2, many of these channels have diverse modulatory factors that couple to PIP2-dependent gating. Channels in the Kir3 (GIRK) family, in particular, have several co-activating elements, including G-protein betagamma subunits, ethanol, and sodium. During stimulation of Gq-coupled receptors, downstream activation of Protein Kinase C can phosphorylate and inhibit Kir3 channels, yet the mechanism of inhibition and phosphorylation sites are incompletely understood. We took a combined …
The Effects Of Neurotensin On The Rat Distal Colon, Rick Chainani
The Effects Of Neurotensin On The Rat Distal Colon, Rick Chainani
Theses and Dissertations
The enteric nervous system controls the gut through the release of specific neurotransmitter and neuromodulators at specific sites such as mucosal secretory cell or smooth muscle cell. In the present study, we have examined the response to one of these neurohumoral agents, Neurotensin, in the rat distal colon. Neurotensin is a paracrine and endocrine modulator of the digestive tract. Even though these effects have been seen in colonic preparations, there are very few functional studies of the effects of Neurotensin in the rat colon, especially the distal colon. In the current study we propose the following hypothesis that Neurotensin will …
Paired Interactions Between Kir Channels And Tertiapin-Q, Chul Ho Yang
Paired Interactions Between Kir Channels And Tertiapin-Q, Chul Ho Yang
Theses and Dissertations
Kir channels serve diverse and important roles throughout the human body and malfunctions of these channels are implicated in various channelopathies. Specific inhibitors for different subtypes of Kir channels are not available. However, Tertiapin-Q (TPNQ), a polypeptide isolated from honey bee venom, differentially inhibits certain subtypes of Kir channels with nanomolar affinity: ROMK1 (Kir1.1) and GIRK1/GIRK4 (Kir3.1/Kir3.4). Modification of TPNQ to increase selectivity for target channels bears great therapeutic potential. The in silico studies based on TPNQ-docked channel models, ROMK1_IRK2 (Kir1.1_Kir2.2) and GIRK2 (Kir3.2), predicted specific paired residue interactions and were experimentally validated here. In ROMK1 E123A mutant, the TPNQ …
Beta-Amyloid Inhibition Of Alpha 7 Nicotinic Acetylcholine Receptors And Factors That Potentially Influence The Aî²/Nachr Interaction, Christopher L. Jacobsen
Beta-Amyloid Inhibition Of Alpha 7 Nicotinic Acetylcholine Receptors And Factors That Potentially Influence The Aî²/Nachr Interaction, Christopher L. Jacobsen
Theses and Dissertations
Alzheimer's disease (AD) is a neurodegenerative disorder that manifests in the form of deficiencies in cognitive processes such as memory and learning. The pathological features of AD include hyperphosphorylated tau proteins that form neurofibrillary tangles as well as senile plaques composed primarily of the peptide β-amyloid (Aβ). When present in high concentrations in the brain, Aβ inhibits certain subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) in the hippocampus. The effects of Aβ in the hippocampus have proven to be neurotoxic, resulting in reduced functionality of nAChRs and the subsequent death of neurons in the cholinergic pathway. The early stages of …
Susceptibility Of Apoptotic Cells To Hydrolysis By Spla2: Molecular Basis And Mechanisms Defined, Elizabeth Gibbons
Susceptibility Of Apoptotic Cells To Hydrolysis By Spla2: Molecular Basis And Mechanisms Defined, Elizabeth Gibbons
Theses and Dissertations
Secretory phospholipase A2 hydrolyzes phospholipids at a lipid-water interface, resulting in pro-inflammatory products being released from cell membranes. Healthy cells are resistant to cleavage by this enzyme, but apoptotic cells become susceptible to its activity. Only bilayers with certain characteristics are able to be hydrolyzed. Most recently, studies in this lab have emphasized the idea that the biophysical state of the bilayer (in terms of lipid order, spacing, and fluidity) is relevant in determining the probability of one phospholipid escaping the membrane to be hydrolyzed. Prior to this study, it had been shown that apoptotic cells undergo biophysical alterations that …
S3-S4 Linker Modulation Of Voltage Sensor Relaxation In Voltage Gated Potassium Channels, W. Everett Fox
S3-S4 Linker Modulation Of Voltage Sensor Relaxation In Voltage Gated Potassium Channels, W. Everett Fox
Theses and Dissertations
It is commonly assumed that the voltage dependence for activation of voltage-gated channels is an intrinsic characteristic of the protein that remains unchanged during electrical activity. However, sporadic reports have suggested otherwise by showing that voltage dependence changes in a use-dependent manner resulting in a voltage dependence shift towards negative potentials (Bezanilla et al., 1982; Bruening-Wright and Larsson, 2007; Kuzmenkin et al., 2004; Labro et al., 2012; Larsson and Elinder, 2000; Olcese et al., 1997; Piper et al., 2003; Shirokov et al., 1992). Although the mechanism underlying the shift in voltage dependence remains unclear, this process seems to have two …
The Effects Of Gain Of Function Mutant P53 And P63 On Eps8 And Cxcl5 Expression In Head And Neck Squamous Cell Carcinoma, Rubana Masood
The Effects Of Gain Of Function Mutant P53 And P63 On Eps8 And Cxcl5 Expression In Head And Neck Squamous Cell Carcinoma, Rubana Masood
Theses and Dissertations
Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancers worldwide, with a survival rate of less than 50%. A class of mutant p53, known as gain of function (GOF) mutant p53, has been found to be expressed in tumors in these patients. GOF mutant p53 not only loses the wild type tumor suppressor functions, but also gains aberrant functions that have been linked to tumorigenesis. In this current study, we utilized a model system consisting of cells derived from HNSCC tumors in order to investigate our hypothesis that GOF mutant p53 enhances, and p63 …
A Model For Sensory Neuron Development By Fgf And Notch: A Multifactorial Approach, Jacob Eugene Voelkel
A Model For Sensory Neuron Development By Fgf And Notch: A Multifactorial Approach, Jacob Eugene Voelkel
Theses and Dissertations
The ophthalmic trigeminal placode (opV) exclusively gives rise to sensory neurons. A number of signaling pathways including Wnt, PDGF, FGF, and Notch are all involved in the progression of an undifferentiated cell in the opV placode to a proneural cell in the condensing opV ganglion. However, the regulatory relationships between these signal transduction pathways are still unknown. To determine if FGF activation acts to modulate Notch signaling in the sensory neurogenesis pathway, a novel multifactorial approach was employed: FGF signaling was inhibited in individual cells and globally with simultaneous inactivation of Notch signaling in chick embryos to investigate if FGF …
Intra-Mitochondrial Injury During Ischemia-Reperfusion, Hema Aluri
Intra-Mitochondrial Injury During Ischemia-Reperfusion, Hema Aluri
Theses and Dissertations
Cardiac injury is increased following ischemia-reperfusion. Mitochondria are the “effector organelles” that are damaged during ischemia (ISC) when there is no blood flow. Resumption of metabolism by damaged mitochondria during reperfusion (REP) results in increased cell injury. Current therapeutic interventions to pre-condition and post-condition the heart during ISC are ineffective during certain conditions like aging and diabetes due to defects in the signaling cascades. In contrast, mitochondrial-based strategies are effective in protecting the heart during ISC-REP. Hence direct therapeutic targeting of dysfunctional mitochondria will provide the potential to bypass the upstream signaling defects and intervene directly upon the effector organelle. …
Effects Of Ischemia And Reperfusion On The Local Regulation Of Oxygen Consumption, Tissue Oxygenation And Blood Supply In Rat Skeletal Muscle., Sami Dodhy
Theses and Dissertations
In resting muscle, blood flow is regulated to meet the demand for O2 by the tissue. A modified ischemia (I)/reperfusion(R) investigation was systematically run and PISFO2, PaO2, Q and VO2 were observed. Twenty-nine spinotrapezius muscles from male Sprague-Dawley rats (284±20 grams) were surgically exteriorized for intravital microscopy to test a model relating blood flow, O2 supply and O2 demand. The model can aid in the understanding of the regulation of tissue PO2. The interstitial PO2 (PISFO2) and perivascular PO2 (PaO2) measurements were made using phosphorescence quenching microscopy (PQM). O2 consumption (VO2) values were obtained with a quasi-continuous, flash-synchronized, pressurized airbag …
The Effects Of Tarsh Overexpression On Lung Carcinomas, Young Kim
The Effects Of Tarsh Overexpression On Lung Carcinomas, Young Kim
Theses and Dissertations
Lung cancer arises from epithelial cells that line the air passages of the lungs. It is the second most common malignancy in the United States; trends suggest that over 228,000 new patients will be diagnosed with lung cancer in 2013. Due to the fact that lung cancer is highly aggressive, it has proven difficult to control. The 5-year survival rate has been shown to be only 15.9%, despite the advances made in terms of diagnosis and treatment. Therefore, we are faced with the problem of finding more effective methods that allow for an earlier diagnosis and the improved treatment of …
The Inflammasome In Acute Myocarditis, Harsha Kannan
The Inflammasome In Acute Myocarditis, Harsha Kannan
Theses and Dissertations
Acute myocarditis is an acute inflammatory syndrome characterized by myocardial damage and dysfunction often due to a viral infection followed by a variable development over time. There are currently no specific treatments and standard treatments for heart failure are generally applied. The inflammasome is a recently identified macromolecular structure that occupies a central role in the amplification of the inflammatory response and promotion of cell death during acute and chronic infections. We hypothesized the formation of the inflammasome in acute myocarditis. To investigate, samples of patients were collected from the Cardiomyopathy Registry in Trieste, with 12 cases of biopsy-proven myocarditis …
Characterization Of The Neurotrophic Factor Brain-Derived Neurotrophic Factor (Bdnf) In Intestinal Smooth Muscle Cells, Mohammad Alqudah
Characterization Of The Neurotrophic Factor Brain-Derived Neurotrophic Factor (Bdnf) In Intestinal Smooth Muscle Cells, Mohammad Alqudah
Theses and Dissertations
Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of secreted proteins, which include in addition to BDNF, nerve growth factor (NGF) and neurotrophin 3-6 (NT-3-6). BDNF mediates its functions by activating two cell surface receptors, pan-neurotrophin receptor (P75NTR) and tropomyosin-related kinase B (TrkB) and their downstream intracellular cascades. BDNF is best known for its role in neuronal survival, regulation of neuronal differentiation, migration and activity-dependent synaptic plasticity. However, BDNF is widely expressed in non-neuronal tissues as well. The localization and the function of BDNF in intestinal smooth muscle cells (SMCs) are not well defined. Thus, the main purpose of …
Sildenafil Attenuates Ethanol-Induced Cardiomyocyte Injury And Preserves Cardiac Function Through Protein Kinase G-Dependent Signaling, Gregory R. Sturz
Sildenafil Attenuates Ethanol-Induced Cardiomyocyte Injury And Preserves Cardiac Function Through Protein Kinase G-Dependent Signaling, Gregory R. Sturz
Theses and Dissertations
Background: Ethanol is a cardiotoxic substance that damages the heart by increasing apoptosis, free radical formation and calcium overloading. Consequently, there is an increase in cell death leaving fewer functioning myocytes leading to heart failure. Sildenafil is a phosphodiesterase type-5 (PDE-5) inhibitor approved for treatment of erectile dysfunction. Studies from our lab have demonstrated that PDE-5 inhibition reduces myocardial infarct size and attenuates post-ischemic cardiac dysfunction in both ischemia-reperfusion and permanent coronary artery ligation models. Therefore, in the present study, we hypothesized that treatment with sildenafil will prevent cardiotoxicity associated with acute alcohol exposure by reducing myocyte apoptosis and preserving …
Regulation Of Gastrointestinal Smooth Muscle Function By Hydrogen Sulfide, Ancy Nalli
Regulation Of Gastrointestinal Smooth Muscle Function By Hydrogen Sulfide, Ancy Nalli
Theses and Dissertations
Inhibitory neurotransmitters, chiefly nitric oxide and vasoactive intestinal peptide, cause MLC20 dephosphorylation and muscle relaxation via inhibition of myosin light chain (MLC) kinase and activation of MLC phosphatase. Hydrogen sulfide (H2S) produced as a byproduct by luminal sulfate-reducing commensal bacteria or as an endogenous signaling molecule synthesized from L-cysteine via cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) regulates muscle contraction. However, the role of H2S in the regulation of MLC phosphatase activity and MLC20 phosphorylation is not known. The aim of the present study was to examine the expression of CSE and CBS in smooth muscle cells and to elucidate the molecular …
Studies On The Reaction Of High-Dose Hydroxocobalamin And Ascorbic Acid With Carbon Monoxide: Implications For Treatment Of Carbon Monoxide Poisoning, Joseph Roderique
Studies On The Reaction Of High-Dose Hydroxocobalamin And Ascorbic Acid With Carbon Monoxide: Implications For Treatment Of Carbon Monoxide Poisoning, Joseph Roderique
Theses and Dissertations
Based upon experimental evidence from the 1970’s we proposed that a reduced form of hydroxocobalamin should be capable of producing carbon dioxide (CO2) from carbon monoxide (CO) in blood, and that this conversion should be detectable. Using resonance raman spectroscopy we demonstrated that a mixture of hydroxocobalamin and ascorbic acid could create the reduced form of hydroxocobalamin. We used a closed-loop circulation system with a hollow-fiber membrane oxygenator to produce carboxyhemoglobin. Using sensitive gas monitoring equipment to the gas-out port of the oxygenator we analyzed the CO and CO2 concentrations coming from the oxygenator. The mixture of hydroxocobalamin and ascorbic …
Sphingosine-1-Phosphate And Fingolimod (Fty720) Regulate Icl,Swell In Hl-1 Cardiac Myocytes Via Intracellular Binding And Mitochondrial Ros Production, Pooja Desai
Theses and Dissertations
Swelling-activated Cl− current (ICl,swell) is an outwardly-rectifying current that plays an important role in cardiac electrical activity, cellular volume regulation, apoptosis, and acts as a potential effector of mechanoelectrical feedback. Persistent activation of ICl,swell has been observed in models of cardiovascular disease. We previously suggested sphingosine-1-phosphate (S1P) activates volume-sensitive Cl- current (ICl,swell) by ROS-dependent signaling. S1P and its analog, FTY720 (fingolimod), primarily act via G-protein coupled receptors (S1PR; S1PR1-3 in heart), but several intracellular S1P ligands are known. We investigated how these agents regulate ICl,swell. ICl,swell was elicited by bath S1P (500 nM), FTY720 (S1PR1,3 agonist; 10 μM), and SEW2871 …
Long-Term Depression Of Excitatory Inputs To Gabaergic Neurons In The Ventral Tegmental Area, Philip J. Sandoval
Long-Term Depression Of Excitatory Inputs To Gabaergic Neurons In The Ventral Tegmental Area, Philip J. Sandoval
Theses and Dissertations
Dopamine cells within the ventral tegmental area of the brain are involved in motivation and reward. Drugs of abuse target these dopamine cells altering their activity and plasticity resulting in addiction. While dopamine cell activity is primarily involved in addiction, the GABA neurons in the VTA have also been shown to have an indirect role. By decreasing the activity of the inhibitory GABA inputs onto dopamine neurons abusive drugs can indirectly increase dopamine cell activity resulting in addictive behaviors. However, although GABA neurons are important in the perception of reward, much less is known about how the excitatory inputs to …