Physiology | Open Access Articles | Digital Commons Network™

Sustained Sensitizing Effects Of Tumor Necrosis Factor Alpha On Sensory Nerves In Lung And Airways, Ruei-Lung Lin, Qihai Gu, Mehdi Khosravi, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 hours later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and …

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Complement 3a Receptor In Dorsal Horn Microglia Mediates Pronociceptive Neuropeptide Signaling, Suzanne Doolen, Jennifer Cook, Maureen Riedl, Kelley Kitto, Shinichi Kohsaka, Christopher N. Honda, Carolyn A. Fairbanks, Bradley K. Taylor, Lucy Vulchanova

Physiology Faculty Publications

The complement 3a receptor (C3aR1) participates in microglial signaling under pathological conditions and was recently shown to be activated by the neuropeptide TLQP‐21. We previously demonstrated that TLQP‐21 elicits hyperalgesia and contributes to nerve injury‐induced hypersensitivity through an unknown mechanism in the spinal cord. Here we determined that this mechanism requires C3aR1 and that microglia are the cellular target for TLQP‐21. We propose a novel neuroimmune signaling pathway involving TLQP‐21‐induced activation of microglial C3aR1 that then contributes to spinal neuroplasticity and neuropathic pain. This unique dual‐ligand activation of C3aR1 by a neuropeptide (TLQP‐21) and an immune mediator (C3a) represents a …

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Associative Learning Contributes To The Increased Water Intake Observed After Daily Injections Of Angiotensin Ii, Maggie Postolache, Jessica Santollo, Derek Daniels

Biology Faculty Publications

Daily injections of angiotensin II (AngII) cause a progressive increase of water intake that resembles a classically ascribed non-associative sensitization. Consistent with the presumption that the observed increase in intake was sensitization, we hypothesized that it resulted from a pharmacological interaction between AngII and its receptor. To test this hypothesis, and remove the influence of drinking itself, we implemented a delay in water access after injection of AngII (icv) on four consecutive ‘induction days,’ and then measured intake on the next day (‘test day’) when rats were allowed to drink immediately after AngII. The delay in water access effectively reduced …

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Inhibition Of Post-Transcriptional Steps In Ribosome Biogenesis Confers Cytoprotection Against Chemotherapeutic Agents In A P53-Dependent Manner, Russell T Sapio, Anastasiya N Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J Manna, Natalie Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The p53-mediated nucleolar stress response associated with inhibition of ribosomal RNA transcription was previously shown to potentiate killing of tumor cells. Here, we asked whether targeting of ribosome biogenesis can be used as the basis for selective p53-dependent cytoprotection of nonmalignant cells. Temporary functional inactivation of the 60S ribosome assembly factor Bop1 in a 3T3 cell model markedly increased cell recovery after exposure to camptothecin or methotrexate. This was due, at least in part, to reversible pausing of the cell cycle preventing S phase associated DNA damage. Similar cytoprotective effects were observed after transient shRNA-mediated silencing of Rps19, but not …

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Cib2 Interacts With Tmc1 And Tmc2 And Is Essential For Mechanotransduction In Auditory Hair Cells, Arnaud P. J. Giese, Yi-Quan Tang, Ghanshyam P. Sinha, Michael R. Bowl, Adam C. Goldring, Andrew Parker, Mary J. Freeman, Steve D. M. Brown, Saima Riazuddin, Robert Fettiplace, William R. Schafer, Gregory I. Frolenkov, Zubair M. Ahmed

Physiology Faculty Publications

Inner ear hair cells detect sound through deflection of stereocilia, the microvilli-like projections that are arranged in rows of graded heights. Calcium and integrin-binding protein 2 is essential for hearing and localizes to stereocilia, but its exact function is unknown. Here, we have characterized two mutant mouse lines, one lacking calcium and integrin-binding protein 2 and one carrying a human deafness-related Cib2 mutation, and show that both are deaf and exhibit no mechanotransduction in auditory hair cells, despite the presence of tip links that gate the mechanotransducer channels. In addition, mechanotransducing shorter row stereocilia overgrow in hair cell bundles of …

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Hibernator And Non-Hibernator Responses To Acute Changes In Water Intake, Sydni S. Andruskiewicz

All College Thesis Program, 2016-2019

Hibernating animals undergo dramatic changes in metabolic rates during torpor. One of most notable changes in these animals is the ability to maintain blood pressure and perfuse certain organs. Consequentially, blood perfusion to the kidneys is greatly decreased and the ability to concentrate urine halts. However, about once a week, torpor is interrupted and the animal becomes active to rewarm itself about once a week. This activity induces rapid regeneration of the extracellular osmotic gradient of the kidney, and allows urine to be concentrated. Nonetheless, regaining the extracellular osmotic gradient creates a potentially fatal consequence to the kidney cells. To …

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Constitutive Activation Of Kappa Opioid Receptors At Ventral Tegmental Area Inhibitory Synapses Following Acute Stress., Abigail M Polter, Kelsey Barcomb, Rudy W Chen, Paige M Dingess, Nicholas M Graziane, Travis E Brown, Julie A Kauer

Pharmacology and Physiology Faculty Publications

Stressful experiences potently activate kappa opioid receptors (κORs). κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function. Here we show that at GABAergic synapses on rat VTA dopamine neurons, a single exposure to a brief cold-water swim stress induces prolonged activation of κORs. This is mediated by activation of the receptor during the stressor followed by a persistent, ligand-independent constitutive activation of the κOR itself. This lasting change in function is not seen at κORs at neighboring excitatory synapses, suggesting distinct time courses and mechanisms of regulation of different subsets of κORs. We also …

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Reduced Skeletal Muscle Satellite Cell Number Alters Muscle Morphology After Chronic Stretch But Allows Limited Serial Sarcomere Addition, Matthew C. Kinney, Sudarshan Dayanidhi, Peter B. Dykstra, John J. Mccarthy, Charlotte A. Peterson, Richard L. Lieber

Physiology Faculty Publications

Introduction: Muscles add sarcomeres in response to stretch, presumably to maintain optimal sarcomere length. Clinical evidence from patients with cerebral palsy, who have both decreased serial sarcomere number and reduced satellite cells (SCs), suggests a hypothesis that SCs may be involved in sarcomere addition. Methods: A transgenic Pax7‐DTA mouse model underwent conditional SC depletion, and their soleii were then stretch‐immobilized to assess the capacity for sarcomere addition. Muscle architecture, morphology, and extracellular matrix (ECM) changes were also evaluated. Results: Mice in the SC‐reduced group achieved normal serial sarcomere addition in response to stretch. However, muscle fiber cross‐sectional …

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Micrornas, Heart Failure, And Aging: Potential Interactions With Skeletal Muscle, Kevin A. Murach, John J. Mccarthy

Center for Muscle Biology Faculty Publications

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting mRNAs for degradation or translational repression. MiRNAs can be expressed tissue specifically and are altered in response to various physiological conditions. It has recently been shown that miRNAs are released into the circulation, potentially for the purpose of communicating with distant tissues. This manuscript discusses miRNA alterations in cardiac muscle and the circulation during heart failure, a prevalent and costly public health issue. A potential mechanism for how skeletal muscle maladaptations during heart failure could be mediated by myocardium-derived miRNAs released to the circulation is presented. An overview …

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Myocardial Relaxation Is Accelerated By Fast Stretch, Not Reduced Afterload, Charles S. Chung, Charles W. Hoopes, Kenneth S. Campbell

Physiology Faculty Publications

Fast relaxation of cross-bridge generated force in the myocardium facilitates efficient diastolic function. Recently published research studying mechanisms that modulate the relaxation rate has focused on molecular factors. Mechanical factors have received less attention since the 1980s when seminal work established the theory that reducing afterload accelerates the relaxation rate. Clinical trials using afterload reducing drugs, partially based on this theory, have thus far failed to improve outcomes for patients with diastolic dysfunction. Therefore, we reevaluated the protocols that suggest reducing afterload accelerates the relaxation rate and identified that myocardial relengthening was a potential confounding factor. We hypothesized that the …

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Full-Text Articles in Physiology

Sustained Sensitizing Effects Of Tumor Necrosis Factor Alpha On Sensory Nerves In Lung And Airways, Ruei-Lung Lin, Qihai Gu, Mehdi Khosravi, Lu-Yuan Lee

Physiology Faculty Publications

Complement 3a Receptor In Dorsal Horn Microglia Mediates Pronociceptive Neuropeptide Signaling, Suzanne Doolen, Jennifer Cook, Maureen Riedl, Kelley Kitto, Shinichi Kohsaka, Christopher N. Honda, Carolyn A. Fairbanks, Bradley K. Taylor, Lucy Vulchanova

Physiology Faculty Publications

Associative Learning Contributes To The Increased Water Intake Observed After Daily Injections Of Angiotensin Ii, Maggie Postolache, Jessica Santollo, Derek Daniels

Biology Faculty Publications

Inhibition Of Post-Transcriptional Steps In Ribosome Biogenesis Confers Cytoprotection Against Chemotherapeutic Agents In A P53-Dependent Manner, Russell T Sapio, Anastasiya N Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J Manna, Natalie Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Physiology Faculty Publications

Hibernator And Non-Hibernator Responses To Acute Changes In Water Intake, Sydni S. Andruskiewicz

All College Thesis Program, 2016-2019

Constitutive Activation Of Kappa Opioid Receptors At Ventral Tegmental Area Inhibitory Synapses Following Acute Stress., Abigail M Polter, Kelsey Barcomb, Rudy W Chen, Paige M Dingess, Nicholas M Graziane, Travis E Brown, Julie A Kauer

Pharmacology and Physiology Faculty Publications

Reduced Skeletal Muscle Satellite Cell Number Alters Muscle Morphology After Chronic Stretch But Allows Limited Serial Sarcomere Addition, Matthew C. Kinney, Sudarshan Dayanidhi, Peter B. Dykstra, John J. Mccarthy, Charlotte A. Peterson, Richard L. Lieber

Physiology Faculty Publications

Micrornas, Heart Failure, And Aging: Potential Interactions With Skeletal Muscle, Kevin A. Murach, John J. Mccarthy

Center for Muscle Biology Faculty Publications

Myocardial Relaxation Is Accelerated By Fast Stretch, Not Reduced Afterload, Charles S. Chung, Charles W. Hoopes, Kenneth S. Campbell

Physiology Faculty Publications