Physiology Commons^™

Review Of Physical Activity Benefits And Potential Considerations For Individuals With Surgical Fusion Of Spine For Scoliosis, Rumit S. Kakar, Kathy J. Simpson, Bhibha M. Das, Cathleen N. Brown

International Journal of Exercise Science

International Journal of Exercise Science 10(2): 166-177, 2017 Evidence-based recommendations for physical activity following spinal fusion surgeries for idiopathic scoliosis are limited, specifically in the adolescent population. Individuals with scoliosis treated operatively or non-operatively have been reported to participate in less than 1-3 days/week of even mildly strenuous physical exercises. Over 40% of individuals with scoliosis returned to sports at a level lower than pre-operative participation levels or did not return at all post spinal fusion. It is particularly important for human movement specialists, such as physical therapists, occupational therapists, athletic trainers and kinesiologists to assist these individuals effectively transition …

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 …

Chemogenetic Stimulation Of The Hypoglossal Neurons Improves Upper Airway Patency, Thomas Curado, Kenneth Fishbein, Huy Pho, Michael Brennick, Olga Dergacheva, David Mendelowitz, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons. DREADD (rAAV5-hSyn-hM3(Gq)-mCherry) and control virus (rAAV5-hSyn-EGFP) were stereotactically administered to the hypoglossal nucleus of C57BL/6J mice. In 6–8 weeks genioglossus EMG and dynamic MRI …

Oxidative Stress-Driven Parvalbumin Interneuron Impairment As A Common Mechanism In Models Of Schizophrenia, P Steullet, J Cabungcal, J Coyle, M Didriksen, K Gill, Anthony-Samuel Lamantia, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant …

Using A Respiratory Navigator Significantly Reduces Variability When Quantifying Left Ventricular Torsion With Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Kristin N. Andres, David K. Powell, Richard J. Charnigo, Brandon K. Fornwalt

Electrical and Computer Engineering Faculty Publications

Background: Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion.

Methods: We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure …

The Insulin-Like Growth Factor-1 (Igf1) System As A Potential Biomarker For Nutritional Status And Growth Rate In Pacific Rockfish (Sebastes Spp.), Nicole L. Hack

Master's Theses

Growth performance in vertebrates is regulated by environmental factors including the quality and quantity of food, which influences growth via endocrine pathways such as the growth hormone (GH) / insulin-like growth factor somatotropic axis. In several teleost fishes, circulating concentrations of insulin-like growth factor-1 (Igf1) correlate positively with growth rate, and it has been proposed that plasma Igf1 levels may serve as an indicator of growth variation for fisheries and aquaculture applications. Here, I tested whether plasma Igf1 concentrations might serve as an indicator of somatic growth in olive rockfish (Sebastes serranoides), one species among dozens of rockfishes …

The Feasibility Of Using The Super Tracker Website For Behavior Changes In The Adolescent Population, Ebony Taylor, Diana Cuy Castellanos

Health and Sport Science Faculty Publications

Research suggests technology such as health websites may be a viable way to effect lifestyle behavior and promote health. Several websites utilize self-monitoring of physical activity and diet as well as provide health-related education as a method to impact behavior. One such site is the Super Tracker tool on ChooseMyPlate.gov, created by the United States Department of Health. The site was created to encourage healthy diet and physical activity within the US population. Therefore, the aim of this original research was to examine the acceptability and feasibility outcomes of a self-monitoring physical activity intervention delivered by the Super Tracker website …

Plasma Metabolites Reveal Changes In Physiological State Of Eared Grebes (Podiceps Nigricollis) During Three Non-Migratory Periods, Allison A. Yoshida

Theses

Energy storage and use during the annual cycle of migratory birds is dynamic especially during migration. However, considerable amounts of the annual cycle are spent not migrating, and the physiological state of birds during these non-migratory periods is not well understood. We compared plasma metabolites (TRIG, BUTY, URIC, GLY) in Eared Grebes (Podiceps nigricollis) residing at three important areas when they are not migrating: fall staging (postbreeding at Mono Lake, California), spring staging (pre-breeding at Great Salt Lake, Utah), and an extended stopover prior to spring staging (Salton Sea, California). Plasma metabolites were also measured in resting and active grebes …

Pre-Training Muscle Characteristics Of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness, Charles A. Stuart, Michelle L. Lee, Mark A. South, Mary E. A. Howell, Brian M. Cartwright, Michael W. Ramsey, Michael H. Stone

ETSU Faculty Works

Pre-training muscle characteristics of subjects who are obese determine how well exercise training will improve their insulin responsiveness. J Strength Cond Res 31(3): 798–808, 2017—Only half of prediabetic subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pretraining characteristics favoring a positive response to exercise training. Thirty nondiabetic subjects who were obese volunteered for 8 weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition, …

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 …

Alterations In Tight Junctional Proteins And Their Effects On Pulmonary Inflammation, Joshua B. Lewis

Theses and Dissertations

The lungs represent one of the earliest interfaces for pathogens and noxious stimuli to interact with the body. As such, careful maintenance of the permeability barrier is vital in providing homeostasis within the lung. Essential to maintaining this barrier is the tight junction, which primarily acts as a paracellular seal and regulator of ionic transport, but also contributes to establishing cell polarity, cell-to-cell integrity, and regulating cell proliferation and differentiation. The loss of these tight junctions has been documented to result in alterations in inflammation, and ultimately the development of many respiratory disorders such as COPD, Asthma, ARDS, and pulmonary …

Phenotypically Heterogeneous Podoplanin-Expressing Cell Populations Are Associated With The Lymphatic Vessel Growth And Fibrogenic Responses In The Acutely And Chronically Infarcted Myocardium, M Cimini, A Cannata, G Pasquinelli, Marcello Rota, P Goichberg

NYMC Faculty Publications

Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts. Podoplanin immunoreactivity detected LYVE-1-positive lymphatic vessels, as well as masses of …

Lkb1 Regulation Of High-Fat Diet-Induced Adaptation In Mouse Skeletal Muscle, Ting Chen

Theses and Dissertations

Ad libitum high-fat diet (HFD)-induced obesity leads to insulin resistance in skeletal muscle, altered gene expression, and altered growth signaling, all of which contributes to pathological changes in metabolism. Liver kinase B1 (LKB1) is an important metabolism regulator. The purpose of this dissertation was to understand how knocking out LKB1 influences HFD induced adaptations in mouse skeletal muscle. To do so, control and skeletal muscle LKB1 knock-out (LKB1-KO) mice were put on either standard diet (STD) or HFD for 1 week or 14 weeks, or put on the HFD for 14 weeks and then switched to STD for 1 week …

Boosting Of Hiv Envelope Cd4 Binding Site Antibodies With Long Variable Heavy Third Complementarity Determining Region In The Randomized Double Blind Rv305 Hiv-1 Vaccine Trial, David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman

Dartmouth Scholarship

The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1- uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 …

Gait Changes In A Line Of Mice Artificially Selected For Longer Limbs, Leah M. Sparrow, Emily Pellattt, Sabrina S. Yu, David A. Raichlen, Herman Pontzer, Campbell Rolian

Publications and Research

In legged terrestrial locomotion, the duration of stance phase, i.e., when limbs are in contact with the substrate, is positively correlated with limb length, and negatively correlated with the metabolic cost of transport. These relationships are well documented at the interspecific level, across a broad range of body sizes and travel speeds. However, such relationships are harder to evaluate within species (i.e., where natural selection operates), largely for practical reasons, including low population variance in limb length, and the presence of confounding factors such as body mass, or training. Here, we compared spatiotemporal kinematics of gait in Longshanks, a long-legged …

Bioaccumulation Of Metallic Trace Elements And Antioxidant Enzyme Activities In Apfelbeckia Insculpta (L. Koch, 1867) (Diplopoda: Callipodida) From The Cave Hadži-Prodanova Pećina (Serbia), Jelena Vranković, Slavica Borković-Mitić, Bojan Ilić, Milanka Radulović, Slaviša Milošević, Slobodan Makarov, Bojan Mitić

International Journal of Speleology

The concentration of 10 metallic trace elements or MTE (Cu, Fe, Zn, Mn, As, Hg, Pb, Cd, Ni, and Cr) was measured in specimens of the troglophilic millipede Apfelbeckia insculpta (L. Koch, 1867) and sediment of the cave Hadži-Prodanova Pećina in western Serbia. Some MTE, like Fe and Mn, displayed much higher concentrations compared to other elements, both in the sediment and in the body of A. insculpta. On the other hand, estimation of the bioaccumulation factor (BAF) in both males and females of A. insculpta showed values greater than 1 for xenobiotic elements compared to those that are essential. …

Blubber Transciptome Response To Acute Stress Axis Activation Involves Transient Charges In Adipogenesis And Lipolysis In Fast-Adapted Marine Mammal, J. I. Khudyakov, C. D. Champagne, L. M. Meneghetti, D. E. Crocker

Biological Sciences Faculty Publications

Stress can compromise an animal's ability to conserve metabolic stores and participate in energy-demanding activities that are critical for fitness. Understanding how wild animals, especially those already experiencing physiological extremes (e.g. fasting), regulate stress responses is critical for evaluating the impacts of anthropogenic disturbance on physiology and fitness, key challenges for conservation. However, studies of stress in wildlife are often limited to baseline endocrine measurements and few have investigated stress effects in fasting-adapted species. We examined downstream molecular consequences of hypothalamic-pituitary-adrenal (HPA) axis activation by exogenous adrenocorticotropic hormone (ACTH) in blubber of northern elephant seals due to the ease of …

Editing Of Misaminoacylated Trna Controls The Sensitivity Of Amino Acid Stress Responses In Saccharomyces Cerevisiae, Kyle Mohler, Rebecca Mann, Tammy J. Bullwinkle, Kyle W. Hopkins, Lin Hwang, Noah M. Reynolds, Brandon Gassaway, Hans-Rudolph Aerni, Jesse Rinehart, Michael Polymenis, Kym F. Faull, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Amino acid starvation activates the protein kinase Gcn2p, leading to changes in gene expression and translation. Gcn2p is activated by deacylated tRNA, which accumulates when tRNA aminoacylation is limited by lack of substrates or inhibition of synthesis. Pairing of amino acids and deacylated tRNAs is catalyzed by aminoacyl-tRNA synthetases, which use quality control pathways to maintain substrate specificity. Phenylalanyl-tRNA synthetase (PheRS) maintains specificity via an editing pathway that targets non-cognate Tyr-tRNA^Phe. While the primary role of aaRS editing is to prevent misaminoacylation, we demonstrate editing of misaminoacylated tRNA is also required for detection of amino acid starvation by …

Serum Comp And The Inflammatory Environment Of The Knee Before And After Exercise-Induced Load, Alyssa Evans, Robert D. Hyldahl, Sarah T. Ridge, Sunku Kwon, Ty J. Hopkins, Eric R. Robinson, Matthew K. Seeley

Biomedical Engineering Western Regional Conference

The purpose of this study was to determine how accurately serum COMP represents inflammatory cytokine levels, within the knee, before and after exercise.

Cytokines included: GM-CSF, IFNa2, IL-10, IL-12p40, IL-13, IL-15, IL-1ra, IL1b, IL1a, IL-4, IL-6, IL-8, IP-10, MCP-1, MIP-1a, MIP-1b and IL-17.

Genetic Targeting In Cerebellar Purkinje Cells: An Update., Anna Sługocka, Jan Wiaderkiewicz, Jaroslaw J Barski

Pharmacology and Physiology Faculty Publications

Since the last review paper published in Cerebellum in 2002 [1], there has been a substantial increase in the number of experiments utilizing transgenic manipulations in murine cerebellar Purkinje cells. Most of these approaches were made possible with the use of the Cre/loxP methodology and pcp2/L7 based Cre recombinase expressing transgenic mouse strains. This review aims to summarize all studies which used Purkinje cell specific transgenesis since the first use of mouse strain with Purkinje cell specific Cre expression in 2002.

Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van Der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal

Genomics and Precision Medicine Faculty Publications

Dystrophin deficiency is the genetic basis for Duchenne muscular dystrophy (DMD), but the cellular basis of progressive myofiber death in DMD is not fully understood. Using two dystrophin-deficient mdx mouse models, we find that the mitochondrial dysfunction is among the earliest cellular deficits of mdx muscles. Mitochondria in dystrophic myofibers also respond poorly to sarcolemmal injury. These mitochondrial deficits reduce the ability of dystrophic muscle cell membranes to repair and are associated with a compensatory increase in dysferlin-mediated membrane repair proteins. Dysferlin deficit in mdx mice further compromises myofiber cell membrane repair and enhances the muscle pathology at an asymptomatic …

Gestational Diabetes Mellitus And The Predisposing Factors, Syeda Sadia Fatima, Rehana Rehman, Faiza Alam, Sarosh Madhani, Bushra Chaudhry, Taseer Ahmed Khan

Department of Biological & Biomedical Sciences

Objective: To evaluate the occurrence of gestational diabetes mellitus and its association with demographic and anthropometric variables in pregnant women.
Methods: This cross-sectional study was conducted at the Aga Khan University Hospital, Abbasi Shaheed Hospital and Memon Hospital in Karachi, from February 2014 to December 2015, and comprised pregnant women who were screened by 75-g 2-hour oral glucose tolerance test, (24-28 weeks of gestation) and classified as per the criteria of the International Association of Diabetes and Pregnancy Study Group. Weight, body mass index and serum glycated haemoglobin levels were measured. Women with pre-gestational diabetes were excluded. SPSS 21 was …

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 …

Quality Control By Isoleucyl-Trna Synthetase Of Bacillus Subtilis Is Required For Efficient Sporulation, Elizabeth Kermgard, Zhou Yang, Annika-Marisa Michel, Rachel Simari, Jacqueline Wong, Michael Ibba, Beth A. Lazazzera

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Isoleucyl-tRNA synthetase (IleRS) is an aminoacyl-tRNA synthetase whose essential function is to aminoacylate tRNA^Ile with isoleucine. Like some other aminoacyl-tRNA synthetases, IleRS can mischarge tRNA^Ile and correct this misacylation through a separate post-transfer editing function. To explore the biological significance of this editing function, we created a ileS(T233P) mutant of Bacillus subtilis that allows tRNA^Ile mischarging while retaining wild-type Ile-tRNA^Ile synthesis activity. As seen in other species defective for aminoacylation quality control, the growth rate of the ileS(T233P) strain was not significantly different from wild-type. When the ileS(T233P) strain was assessed for its ability to promote …

Transforming Growth Factor-Β In Thoracic Aortic Aneurysms: Good, Bad, Or Irrelevant?, Alan Daugherty, Zheying Chen, Hisashi Sawada, Debra L. Rateri, Mary B. Sheppard

Physiology Faculty Publications

No abstract provided.

Ms-Read: Quantitative Measurement Of Amino Acid Incorporation, Kyle Mohler, Hans-Rudolph Aerni, Brandon Gassaway, Jiqiang Ling, Michael Ibba, Jesse Rinehart

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Ribosomal protein synthesis results in the genetically programmed incorporation of amino acids into a growing polypeptide chain. Faithful amino acid incorporation that accurately reflects the genetic code is critical to the structure and function of proteins as well as overall proteome integrity. Errors in protein synthesis are generally detrimental to cellular processes yet emerging evidence suggest that proteome diversity generated through mistranslation may be beneficial under certain conditions. Cumulative translational error rates have been determined at the organismal level, however codon specific error rates and the spectrum of misincorporation errors from system to system remain largely unexplored. In particular, until …

Novel Interconnections In Lipid Metabolism Revealed By Overexpression Of Sphingomyelin Synthase-1, Gergana M. Deevska, Patrick P. Dotson Ii, Alexander A. Karakashian, Giorgis Isaac, Mark Wrona, Samuel B. Kelly, Alfred H. Merrill Jr., Mariana N. Nikolova‑Karakashian

Physiology Faculty Publications

This study investigates the consequences of elevating sphingomyelin synthase 1 (SMS1) activity, which generates the main mammalian sphingolipid, sphingomyelin. HepG2 cells stably transfected with SMS1 (HepG2-SMS1) exhibit elevated enzyme activity in vitro and increased sphingomyelin content (mainly C22:0- and C24:0-sphingomyelin) but lower hexosylceramide (Hex-Cer) levels. HepG2-SMS1 cells have fewer triacylglycerols than controls but similar diacylglycerol acyltransferase activity, triacylglycerol secretion, and mitochondrial function. Treatment with 1 mm palmitate increases de novo ceramide synthesis in both cell lines to a similar degree, causing accumulation of C16:0-ceramide (and some C18:0-, C20:0-, and C22:0-ceramides) as well as C16:0- and C18:0-Hex-Cers. In these experiments, the …

Omecamtiv Mecarbil Enhances The Duty Ratio Of Human Β-Cardiac Myosin Resulting In Increased Calcium Sensitivity And Slowed Force Development In Cardiac Muscle, Anja M. Swenson, Wanjian Tang, Cheavar A. Blair, Christopher M. Fetrow, William C. Unrath, Michael J. Previs, Kenneth S. Campbell, Christopher M. Yengo

Physiology Faculty Publications

The small molecule drug omecamtiv mecarbil (OM) specifically targets cardiac muscle myosin and is known to enhance cardiac muscle performance, yet its impact on human cardiac myosin motor function is unclear. We expressed and purified human β-cardiac myosin subfragment 1 (M2β-S1) containing a C-terminal Avi tag. We demonstrate that the maximum actin-activated ATPase activity of M2β-S1 is slowed more than 4-fold in the presence of OM, whereas the actin concentration required for half-maximal ATPase was reduced dramatically (30-fold). We find OM does not change the overall actin affinity. Transient kinetic experiments suggest that there are …

Fröhlich Effect And Delays Of Visual Attention, Nika Adamian, Patrick Cavanagh

Dartmouth Scholarship

In the Fröhlich effect, the initial position of an object that suddenly appears in motion is perceived as being shifted in the direction of its motion. Here we establish that this shift is not an obligatory consequence of motion, but it is driven by focused attention. In Experiment 1 using different cueing conditions, we found that invalid cues produced larger perceptual shifts, although the Fröhlich effect was still present for valid and neutral cues. These results support Müsseler and Aschersleben's (1998) proposal that the Fröhlich effect is the result of the time it takes to shift focal attention to the …

Diaphragm Abnormalities In Patients With End-Stage Heart Failure: Nadph Oxidase Upregulation And Protein Oxidation, Bumsoo Ahn, Philip D. Coblentz, Adam W. Beharry, Nikhil Patel, Andrew R. Judge, Jennifer S. Moylan, Charles W. Hoopes, Mark R. Bonnell, Leonardo F. Ferreira

Physiology Faculty Publications

Patients with heart failure (HF) have diaphragm abnormalities that contribute to disease morbidity and mortality. Studies in animals suggest that reactive oxygen species (ROS) cause diaphragm abnormalities in HF. However, the effects of HF on ROS sources, antioxidant enzymes, and protein oxidation in the diaphragm of humans is unknown. NAD(P)H oxidase, especially the Nox2 isoform, is an important source of ROS in the diaphragm. Our main hypothesis was that diaphragm from patients with HF have heightened Nox2 expression and p47^phox phosphorylation (marker of enzyme activation) that is associated with elevated protein oxidation. We collected diaphragm biopsies from patients with …