Physiology Commons^™

Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén

Physiology Faculty Publications

AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP).

METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were …

Mechanisms Of Statin Effects On Muscle And Neuronal Proteostasis, Daniel Yu

University Scholar Projects

Statins are widely prescribed and used chronically, but we know little about the effects on long-term protein homeostasis during stress and aging. Our aim was to quantify the effect of statins on stress-induced protein damage. We administered atorvastatin in a dose-response curve in Caenorhabditis elegans under naïve control conditions and in conditions of hypertonic and heat stress known to induce muscle damage measurable as countable puncta in a polyglutamine aggregation model of damage. We observed that there is significant polyglutamine aggregation variability among worms at baseline and thus further study requires within experiment baseline controls, per worm. Our results are …

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …

Phase- Specific Changes In Rate Of Force Development And Muscle Morphology Throughout A Block Periodized Training Cycle In Weightlifters, Dylan G. Suarez, Satoshi Mizuguchi, William Guy Hornsby, Aaron J. Cunanan, Donald J. Marsh, Michael H. Stone

ETSU Faculty Works

The purpose of this study was to investigate the kinetic and morphological adaptations that occur during distinct phases of a block periodized training cycle in weightlifters. Athlete monitoring data from nine experienced collegiate weightlifters was used. Isometric mid-thigh pull (IMTP) and ultrasonography (US) results were compared to examine the effects of three specific phases of a training cycle leading up to a competition. During the high volume strength-endurance phase (SE) small depressions in rate of force development (RFD) but statistically significant (p ≤ 0.05) increases in vastus lateralis cross-sectional area (CSA), and body mass (BM) were observed. The lower volume …

Tutorial For Using Sliceomatic To Calculate Thigh Area And Composition From Computed Tomography Images From Older Adults, Richard A. Dennis, Douglas E. Long, Reid D. Landes, Kalpana P. Padala, Prasad R. Padala, Kimberly K. Garner, James N. Wise, Charlotte A. Peterson, Dennis H. Sullivan

Center for Muscle Biology Faculty Publications

Objective

Area of muscle, fat, and bone is often measured in thigh CT scans when tissue composition is a key outcome. SliceOmatic software is commonly referenced for such analysis but published methods may be insufficient for new users. Thus, a quick start guide to calculating thigh composition using SliceOmatic has been developed.

Methods

CT images of the thigh were collected from older (69 ± 4 yrs, N = 24) adults before and after 12-weeks of resistance training. SliceOmatic was used to segment images into seven density regions encompassing fat, muscle, and bone from -190 to +2000 Hounsfield Units [HU]. The …

Myogenic Progenitor Cells Control Extracellular Matrix Production By Fibroblasts During Skeletal Muscle Hypertrophy, Christopher S. Fry, Tyler J. Kirby, Kate Kosmac, John J. Mccarthy, Charlotte A. Peterson

Physiology Faculty Publications

Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. …

Enhancement Of Aging Rat Laryngeal Muscles With Endogenous Growth Factor Treatment, Joseph C. Stemple, Richard D. Andreatta, Tanya S. Seward, Vrushali Angadi, Maria Dietrich, Colleen A. Mcmullen

Physical Therapy Faculty Publications

Clinical evidence suggests that laryngeal muscle dysfunction is associated with human aging. Studies in animal models have reported morphological changes consistent with denervation in laryngeal muscles with age. Life‐long laryngeal muscle activity relies on cytoskeletal integrity and nerve–muscle communication at the neuromuscular junction (NMJ). It is thought that neurotrophins enhance neuromuscular transmission by increasing neurotransmitter release. We hypothesized that treatment with neurotrophin 4 (NTF4) would modify the morphology and functional innervation of aging rat laryngeal muscles. Fifty‐six Fischer 344xBrown Norway rats (6‐ and 30‐mo age groups) were used to evaluate to determine if NTF4, given systemically (n = 32) …

The Development Of Skeletal Muscle In Young Horses: An Ultrasonography And Satellite Cell Approach, Emma K. Lavigne

Honors Scholar Theses

Muscle growth in young horses is characterized by an increase in muscle cross-sectional area, which can be accomplished through the activation and differentiation of satellite cells. Satellite cells can be stimulated or inhibited in response to different cytokines and growth factors and are key mediators of muscle hypertrophy and regeneration. The aim of this study was to investigate the growth of the longissimus dorsi (LD) muscle in horses under 5 years of age and to obtain preliminary data on satellite cell behavior in foals. The area, width, height, and subcutaneous fat were measured using ultrasonography at 6-month increments over the …

Smooth-Muscle Bmal1 Participates In Blood Pressure Circadian Rhythm Regulation, Zhongwen Xie, Wen Su, Shu Liu, Guogang Zhao, Karyn Esser, Elizabeth A. Schroder, Mellani Lefta, Harald M. Stauss, Zhenheng Guo, Ming Cui Gong

Physiology Faculty Publications

As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock genes in the circadian rhythm of blood pressure remains uncertain. Here, we demonstrate that selective deletion of the circadian clock transcriptional activator aryl hydrocarbon receptor nuclear translocator-like (Bmal1) from smooth muscle, but not from cardiomyocytes, compromised blood pressure circadian rhythm and decreased blood …

Bracing Of The Trunk And Neck Has A Differential Effect On Head Control During Gait, S. Morrison, D. M. Russell, K. Kelleran, M. L. Walker

Rehabilitation Sciences Faculty Publications

During gait, the trunk and neck are believed to play an important role in dissipating the transmission of forces from the ground to the head. This attenuation process is important to ensure head control is maintained. The aim of the present study was to assess the impact of externally restricting the motion of the trunk and/or neck segments on acceleration patterns of the upper body and head and related trunk muscle activity. Twelve healthy adults performed three walking trials on a flat, straight 65-m walkway, under four different bracing conditions: 1) control-no brace; 2) neck-braced; 3) trunk-braced; and 4) neck-trunk …

Insulin Resistance And Muscle Insulin Receptor Substrate-1 Serine Hyperphosphorylation, Charles A. Stuart, Mary E. A. Howell, Brian M. Cartwright, Melanie P. Mccurry, Michelle L. Lee, Michael W. Ramsey, Michael H. Stone

ETSU Faculty Works

Insulin resistance in metabolic syndrome subjects is profound in spite of muscle insulin receptor and insulin-responsive glucose transporter (GLUT4) expression being nearly normal. Insulin receptor tyrosine kinase phosphorylation of insulin receptor substrate-1 (IRS-1) at Tyr896 is a necessary step in insulin stimulation of translocation of GLUT4 to the cell surface. Serine phosphorylation of IRS-1 by some kinases diminishes insulin action in mice. We evaluated the phosphorylation status of muscle IRS-1 in 33 subjects with the metabolic syndrome and seventeen lean controls. Each underwent euglycemic insulin clamps and a thigh muscle biopsy before and after 8 weeks of either strength or …

Neutral Sphingomyelinase-3 Mediates Tnf-Stimulated Oxidant Activity In Skeletal Muscle, Jennifer S. Moylan, Jeffrey D. Smith, Erin M. Wolf Horrell, Julie B. Mclean, Gergana M. Deevska, Mark R. Bonnell, Mariana N. Nikolova‑Karakashian, Michael B. Reid

Physiology Faculty Publications

AIMS: Sphingolipid and oxidant signaling affect glucose uptake, atrophy, and force production of skeletal muscle similarly and both are stimulated by tumor necrosis factor (TNF), suggesting a connection between systems. Sphingolipid signaling is initiated by neutral sphingomyelinase (nSMase), a family of agonist-activated effector enzymes. Northern blot analyses suggest that nSMase3 may be a striated muscle-specific nSMase. The present study tested the hypothesis that nSMase3 protein is expressed in skeletal muscle and functions to regulate TNF-stimulated oxidant production.

RESULTS: We demonstrate constitutive nSMase activity in skeletal muscles of healthy mice and humans and in differentiated C2C12 myotubes. nSMase3 ( …

Ipla2Β Overexpression In Smooth Muscle Exacerbates Angiotensin Ii-Induced Hypertension And Vascular Remodeling, Lindsay E Calderon, Shu Liu, Wen Su, Zhongwen Xie, Zhenheng Guo, Wanda Eberhard, Ming C. Gong

Physiology Faculty Publications

OBJECTIVES: Calcium independent group VIA phospholipase A₂ (iPLA₂β) is up-regulated in vascular smooth muscle cells in some diseases, but whether the up-regulated iPLA₂β affects vascular morphology and blood pressure is unknown. The current study addresses this question by evaluating the basal- and angiotensin II infusion-induced vascular remodeling and hypertension in smooth muscle specific iPLA₂β transgenic (iPLA₂β-Tg) mice.

METHOD AND RESULTS: Blood pressure was monitored by radiotelemetry and vascular remodeling was assessed by morphologic analysis. We found that the angiotensin II-induced increase in diastolic pressure was significantly higher in iPLA₂β-Tg …

Age-Associated Disruption Of Molecular Clock Expression In Skeletal Muscle Of The Spontaneously Hypertensive Rat, Mitsunori Miyazaki, Elizabeth Schroder, Stephanie E. Edelmann, Michael E. Hughes, Karl Kornacker, C. William Balke, Karyn A. Esser

Physiology Faculty Publications

It is well known that spontaneously hypertensive rats (SHR) develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007) linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure) compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including …

A Mathematical Model Of Muscle Containing Heterogeneous Half-Sarcomeres Exhibits Residual Force Enhancement, Stuart G. Campbell, P. Chris Hatfield, Kenneth S. Campbell

Physiology Faculty Publications

A skeletal muscle fiber that is stimulated to contract and then stretched from L₁ to L₂ produces more force after the initial transient decays than if it is stimulated at L₂. This behavior has been well studied experimentally, and is known as residual force enhancement. The underlying mechanism remains controversial. We hypothesized that residual force enhancement could reflect mechanical interactions between heterogeneous half-sarcomeres. To test this hypothesis, we subjected a computational model of interacting heterogeneous half-sarcomeres to the same activation and stretch protocols that produce residual force enhancement in real preparations. Following a transient period of elevated force associated with …

Mip/Mtmr14 And Muscle Aging, Scott K. Powers, Michael B. Reid

Physiology Faculty Publications

No abstract.

Genomic Profiling Of Messenger Rnas And Micrornas Reveals Potential Mechanisms Of Tweak-Induced Skeletal Muscle Wasting In Mice, Siva K. Panguluri, Shephali Bhatnagar, Akhilesh Kumar, John J. Mccarthy, Apurva K. Srivastava, Nigel G. Cooper, Robert F. Lundy, Ashok Kumar

Physiology Faculty Publications

BACKGROUND: Skeletal muscle wasting is a devastating complication of several physiological and pathophysiological conditions. Inflammatory cytokines play an important role in the loss of skeletal muscle mass in various chronic diseases. We have recently reported that proinflammatory cytokine TWEAK is a major muscle-wasting cytokine. Emerging evidence suggests that gene expression is regulated not only at transcriptional level but also at post-transcriptional level through the expression of specific non-coding microRNAs (miRs) which can affect the stability and/or translation of target mRNA. However, the role of miRs in skeletal muscle wasting is unknown.

METHODOLOGY/PRINCIPAL FINDINGS: To understand the mechanism of action of …

Passive Limb Movement Augments Ventilatory Response To Co2 Via Sciatic Inputs In Anesthetized Rats, Jianguo Zhuang, Fadi Xu, Cancan Zhang, Donald T. Frazier

Physiology Faculty Publications

Passive limb movement (PLM) in humans induces a phasic hyperpnea, but the underlying physiological mechanisms remain unclear. We asked whether PLM in anesthetized rats would produce a similar phasic hyperpnea associated with an augmented ventilatory (V̇_E) response to CO₂ that is dependent on sciatic afferents. The animals underwent 5 min threshold PLM, 3 min hypercapnia (5% CO₂), and their combination (CO₂ exposure at the end of 2^nd min of 5-min PLM) before and after bilateral transection of the sciatic nerves. We found that a threshold PLM evoked a phasic hyperpnea, similar to …

A Motor And A Brake: Two Leg Extensor Muscles Acting At The Same Joint Manage Energy Differently In A Running Insect, Anna N. Ahn, Robert J. Full

All HMC Faculty Publications and Research

The individual muscles of a multiple muscle group at a given joint are often assumed to function synergistically to share the load during locomotion. We examined two leg extensors of a running cockroach to test the hypothesis that leg muscles within an anatomical muscle group necessarily manage (i.e. produce, store, transmit or absorb) energy similarly during running. Using electromyographic and video motion-analysis techniques, we determined that muscles 177c and 179 are both active during the first half of the stance period during muscle shortening. Using the in vivo strain and stimulation patterns determined during running, we measured muscle power output. …