DOCSLIB.ORG

YB-1 Stress-Response Protein Conformation Implicated in Post-Transcriptional

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
YB-1 Stress-Response Protein Conformation Implicated in Post-Transcriptional YB-1 Stress-Response Protein Conformation Implicated in Post-transcriptional Control of Myofibroblast Differentiation DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By William L. Willis Graduate Program in Biomedical Science The Ohio State University 2013 Dissertation Committee: Arthur R. Strauch, Ph.D., Advisor Denis C. Guttridge, Ph.D. Lai-Chu Wu, Ph.D. Mark T. Ziolo, Ph.D. Copyright by William L. Willis 2013 Abstract Differentiation of stromal fibroblasts into myofibroblasts is critical for wound healing and tissue repair. Normally a transient process, chronic myofibroblast activation is the leading cause of hypertrophic scarring, loss of tissue compliance, and dysfunctional tissue remodeling. Vascular smooth muscle α-actin (SMαA) is an indicator of myofibroblast differentiation, as well as one of several fetal contractile protein isoforms re-expressed in adult cardiomyocytes in response to mechanical stress-injury. The stress- response protein, Y-box binding protein-1 (YB-1) binds SMαA mRNA and regulates its translational activity. Our central hypothesis is that YB-1 drives maladaptive SMαA expression in injury-activated myofibroblasts by modulating the packaging, delivery, and translational efficiency of its cognate mRNA. In a mouse model for cardiac fibrosis, we observed that accumulation of fetal SMαA protein in cardiac sarcomeres was associated with accumulation of punctate YB-1 deposits which localized to perinuclear regions as well as polyribosome-enriched cytosol proximal to cardiac intercalated discs. Samples from both fibrotic mouse hearts as well as SMαA positive endomyocardial biopsies from human heart transplant patients were enriched with high molecular weight, heat- denaturing resistant YB-1 oligomers migrating in the range of 100-250 kDa during reducing SDS-PAGE. Notably, YB-1 oligomers exhibited selective affinity for an exon- ii 3 derived translation silencer sequence in SMαA mRNA. Presence of p180 YB-1 oligomers in endomyocardial biopsies increased with SMαA protein expression and graft age, suggesting that in addition to monomeric YB-1 p50, p180 oligomers may be a preferred YB-1 size variant for storing/protecting fetal mRNA transcripts during myocardial remodeling. Based on these intriguing observations, which suggested that YB-1 oligomer formation may be associated with the packaging and translation control of SMαA mRNA, we examined the regulatory aspects of YB-1 oligomerization using a model system based on isolated human pulmonary fibroblasts. Activation of SMαA gene expression in human pulmonary myofibroblasts by TGF1 was associated with formation of denaturation- resistant YB-1 oligomers with selective affinity for the SMαA exon-3 translation-silencer sequence. We discovered that YB-1 is a substrate for the protein-crosslinking enzyme transglutaminase 2 (TG2) that catalyzes calcium-dependent formation of covalent - glutamyl-isopeptide linkages in response to reactive oxygen signaling. TG2 transamidation reaction studies using intact cells, cell lysates, and recombinant YB-1 revealed covalent crosslinking of the 50 kDa YB-1 polypeptide into protein oligomers that were distributed during SDS-PAGE over a 75 kDa to 250 kDa size range. In vitro YB-1 transamidation required nanomolar levels of calcium and was enhanced by the presence of SMαA mRNA. YB-1 crosslinking was inhibited by (a) anti-oxidant cystamine, (b) the reactive-oxygen antagonist, diphenyleneiodonium, (c) competitive inhibition of TG2 transamidation using the aminyl-surrogate substrate, iii monodansylcadaverine, and (d) transfection with small-interfering RNA specific for human TG2 mRNA. YB-1 crosslinking was partially reversible as a function of free- calcium concentration and TG2 enzyme availability. Metabolic stress incurred during tissue injury may also promote conversion of resident fibroblasts to the myofibroblast phenotype, as temporary loss of tissue perfusion promotes a hypoxic, energy-deficient pro-oxidative cellular microenvironment. Stimulation of AMPK activity with AICAR activated TG2 transamidation and induced the formation of high molecular weight YB-1 oligomers with enhanced affinity for the SMαA mRNA exon-3 translation-silencer sequence. We found that AMPK and peroxide differentially regulated phosphorylation of the YB-1 cold-shock domain, which modulates YB-1 subcellular localization and SMαA mRNA binding efficiency. AICAR suppressed YB-1 phosphorylation, which prevented nuclear translocation and activated SMαA mRNA binding. In contrast, peroxide stimulation activated Erk/MAPK dependent phosphorylation of the YB-1 cold-shock domain and caused the dispersal of YB-1: SMαA mRNA complexes. Thus, we propose that coordinated early AMPK activation and delayed ROS production during myofibroblast differentiation regulates SMαA expression at the post-transcriptional level, by coordinating the respective packaging and deployment/translation activation of SMαA mRNA from YB-1 ribonucleoprotein complexes. In summary, intracellular calcium accumulation and increased ROS levels incurred during metabolic and biomechanical stress may govern SMαA mRNA iv translational activity during wound healing and cardiopulmonary stress responses via TG2-mediated crosslinking of the YB-1 mRNA-binding protein. v Dedicated to my parents, Pamela and William L. Willis vi Acknowledgments I would like to thank my advisor, Dr. Arthur Strauch, for the opportunity to join his lab. His guidance, insight, and scientific expertise have been invaluable throughout my graduate career, and have greatly contributed to my development as a scientist. I would also like Dr. Lai-Chu Wu for her guidance and expertise during early rotations in her lab. Her guidance, training, and advice during those early days laid foundation for the work I have completed in this dissertation. I would to thank Dr. Denis Guttridge, Dr. Lai-Chu Wu, and Dr. Mark Ziolo for their time serving on my committee and their helpful guidance along the way. Special thanks to Dr. Jason David in the Art Strauch lab who kindly provided training in YB-1 immunoblots and RNA pull-down techniques as well as sharing some data shown in the dissertation that supported the YB-1 oligomerization hypothesis during the early, formative stages of my work. Finally I would like to express my sincerest gratitude to my parents, for the encouragement to continue. vii Vita June 20, 1978 .............................................. Born- W. Palm Beach, FL 2004 ............................................................ B.Sc. Chemistry, The Ohio State University 2006-2008 .................................................. Graduate Research Associate The Ohio State University 2008-present ............................................... Graduate Research Associate, The Ohio State University (In the lab of Dr. Arthur Strauch) Publications 1. Eiring, AM, Neviani P, Santhanam R, Oaks JJ, Chang JS, Notari M, Willis WL, Gambacorti-Passerini C, Violinia S, Marcucci G, Caligiuri MA, Leone GW, Perrotti D. Identification of novel post-transcriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis. Blood 2008 Jan 15;111(2)816-28 2. Hutzen,B.; Willis,WL., Jones,S., Cen,L., Deangelis,S., Fuh,B., Lin,J. Dietary agent, benzyl isothiocyanate inhibits signal transducer and activator of transcription 3 phosphorylation and collaborates with sulforaphane in the growth suppression of PANC-1 cancer cells. Cancer Cell International 2009 Aug 27;9:24 3. Canner,JA., Sobo,M., Ball,S.; Hutzen,B., DeAngelis,S., Willis,WL., Studebaker,A.W., Ding,K., Wang,S.; Yang,D., Lin,J. MI-63: a novel small- molecule inhibitor targets MDM2 and induces apoptosis in embryonal and alveolar rhabdomyosarcoma cells with wild-type p53. British Journal of Cancer 2009 Sep 1;101(5): 774–781 viii 4. David, D.A. Subramanian, S.V, Zhang, A. Willis, WL, Kelm, RJ, Leir, CV, Strauch, AR. Y-Box binding protein-1 implicated in translational control of fetal myocardial gene expression after cardiac transplant. Experimental Biology and Medicine 2012 May1; 237(5): 593-607 5. Willis, WL, Seethalakshmi Hariharan, Jason J. David, Arthur Strauch. Transglutaminase-2 Mediates Calcium-Regulated Crosslinking of the Y-Box 1 (YB-1) Translation-Regulatory Protein in TGFβ1-Activated Myofibroblasts. Journal of Cellular Biochemistry [published online ahead of print June 27, 2013] Fields of Study Major Field: Biomedical Sciences Graduate Program ix Table of Contents Abstract .......................................................................................................................... ii Acknowledgments ........................................................................................................ vii Vita ............................................................................................................................. viii List of Tables................................................................................................................ xii List of Figures ............................................................................................................. xiii Chapter 1: Introduction ....................................................................................................1 Chapter 2: Covalent YB-1 oligomerization is associated with post-transplant cardiac remodeling and fetal smooth muscle α-actin gene reactivation .........................................5 2.1 Introduction ...........................................................................................................5
Load more

Recommended publications
  • Back-To-Basics: the Intricacies of Muscle Contraction
    Back-to- MIOTA Basics: The CONFERENCE OCTOBER 11, Intricacies 2019 CHERI RAMIREZ, MS, of Muscle OTRL Contraction OBJECTIVES: 1.Review the anatomical structure of a skeletal muscle. 2.Review and understand the process and relationship between skeletal muscle contraction with the vital components of the nervous system, endocrine system, and skeletal system. 3.Review the basic similarities and differences between skeletal muscle tissue, smooth muscle tissue, and cardiac muscle tissue. 4.Review the names, locations, origins, and insertions of the skeletal muscles found in the human body. 5.Apply the information learned to enhance clinical practice and understanding of the intricacies and complexity of the skeletal muscle system. 6.Apply the information learned to further educate clients on the importance of skeletal muscle movement, posture, and coordination in the process of rehabilitation, healing, and functional return. 1. Epithelial Four Basic Tissue Categories 2. Muscle 3. Nervous 4. Connective A. Loose Connective B. Bone C. Cartilage D. Blood Introduction There are 3 types of muscle tissue in the muscular system: . Skeletal muscle: Attached to bones of skeleton. Voluntary. Striated. Tubular shape. Cardiac muscle: Makes up most of the wall of the heart. Involuntary. Striated with intercalated discs. Branched shape. Smooth muscle: Found in walls of internal organs and walls of vascular system. Involuntary. Non-striated. Spindle shape. 4 Structure of a Skeletal Muscle Skeletal Muscles: Skeletal muscles are composed of: • Skeletal muscle tissue • Nervous tissue • Blood • Connective tissues 5 Connective Tissue Coverings Connective tissue coverings over skeletal muscles: .Fascia .Tendons .Aponeuroses 6 Fascia: Definition: Layers of dense connective tissue that separates muscle from adjacent muscles, by surrounding each muscle belly.
    [Show full text]
  • Muscle Physiology Dr
    Muscle Physiology Dr. Ebneshahidi Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Skeletal Muscle Figure 9.2 (a) Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Functions of the muscular system . 1. Locomotion . 2. Vasoconstriction and vasodilatation- constriction and dilation of blood vessel Walls are the results of smooth muscle contraction. 3. Peristalsis – wavelike motion along the digestive tract is produced by the Smooth muscle. 4. Cardiac motion . 5. Posture maintenance- contraction of skeletal muscles maintains body posture and muscle tone. 6. Heat generation – about 75% of ATP energy used in muscle contraction is released as heat. Copyright. © 2004 Pearson Education, Inc., publishing as Benjamin Cummings . Striation: only present in skeletal and cardiac muscles. Absent in smooth muscle. Nucleus: smooth and cardiac muscles are uninculcated (one nucleus per cell), skeletal muscle is multinucleated (several nuclei per cell ). Transverse tubule ( T tubule ): well developed in skeletal and cardiac muscles to transport calcium. Absent in smooth muscle. Intercalated disk: specialized intercellular junction that only occurs in cardiac muscle. Control: skeletal muscle is always under voluntary control‚ with some exceptions ( the tongue and pili arrector muscles in the dermis). smooth and cardiac muscles are under involuntary control. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Innervation: motor unit . a) a motor nerve and a myofibril from a neuromuscular junction where gap (called synapse) occurs between the two structures. at the end of motor nerve‚ neurotransmitter (i.e. acetylcholine) is stored in synaptic vesicles which will release the neurotransmitter using exocytosis upon the stimulation of a nerve impulse. Across the synapse the surface the of myofibril contains receptors that can bind with the neurotransmitter.
    [Show full text]
  • Titin N2A Domain and Its Interactions at the Sarcomere
    International Journal of Molecular Sciences Review Titin N2A Domain and Its Interactions at the Sarcomere Adeleye O. Adewale and Young-Hoon Ahn * Department of Chemistry, Wayne State University, Detroit, MI 48202, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-(313)-577-1384 Abstract: Titin is a giant protein in the sarcomere that plays an essential role in muscle contraction with actin and myosin filaments. However, its utility goes beyond mechanical functions, extending to versatile and complex roles in sarcomere organization and maintenance, passive force, mechanosens- ing, and signaling. Titin’s multiple functions are in part attributed to its large size and modular structures that interact with a myriad of protein partners. Among titin’s domains, the N2A element is one of titin’s unique segments that contributes to titin’s functions in compliance, contraction, structural stability, and signaling via protein–protein interactions with actin filament, chaperones, stress-sensing proteins, and proteases. Considering the significance of N2A, this review highlights structural conformations of N2A, its predisposition for protein–protein interactions, and its multiple interacting protein partners that allow the modulation of titin’s biological effects. Lastly, the nature of N2A for interactions with chaperones and proteases is included, presenting it as an important node that impacts titin’s structural and functional integrity. Keywords: titin; N2A domain; protein–protein interaction 1. Introduction Citation: Adewale, A.O.; Ahn, Y.-H. The complexity of striated muscle is defined by the intricate organization of its com- Titin N2A Domain and Its ponents [1]. The involuntary cardiac and voluntary skeletal muscles are the primary types Interactions at the Sarcomere.
    [Show full text]
  • Muscular System ANS 215 Physiology and Anatomy of Domesticated Animals
    Muscular System ANS 215 Physiology and Anatomy of Domesticated Animals I. Skeletal Muscle Contraction A. Neuromuscular junction functions as an amplifier for a nerve impulse B. Arrival of a spinal or cranial nerve impulse at the neuromuscular junction results in release of acetylcholine (Ach) into the space between the nerve fiber terminal branch and the muscle fiber C. Release of Ach is accelerated because Ca ions from extracellular fluid enter the prejunctional membrane when the nerve impulse arrives D. Ach is the stimulus that increases the permeability of the muscle fiber membrane for Na ions, after which depolarization begins E. Depolarization proceeds in all directions from the neuromuscular junction F. Impulse is conducted into all parts of the muscle fiber by the sarcotubular system (synchronizes muscle fiber contraction) G. Low concentration of Ca in the extracellular fluid is recognized clinically in dairy cows after calving (parturient paresis) as a state of semi-paralysis caused by partial neuromuscular block. H. Almost immediately after its release Ach is hydrolyzed by the enzyme acetylcholinesterase into acetic acid and choline I. Next depolarization must await the arrival of the next nerve impulse J. Tubules of sarcoplasmic reticulum have a relatively high concentration of Ca ions K. Depolarization of these tubules results in a simultaneous release of Ca ions into the sarcoplasm, which in turn diffuse rapidly into the myofibrils L. Presence of Ca ions within the myofibrils initiates the contraction process M. The Ca ions are returned rapidly by active transport to the sarcoplasmic reticulum after contraction is initiated and are released again when the next signal arrives.
    [Show full text]
  • Histology of Muscle Tissue
    HISTOLOGY OF MUSCLE TISSUE Dr. Sangeeta Kotrannavar Assistant Professor Dept. of Anatomy, USM-KLE IMP, Belagavi Objectives Distinguish the microscopic features of • Skeletal • Cardiac • Smooth muscles Muscle • Latin musculus =little mouse (mus) • Muscle cells are known as MYOCYTES. • Myocytes are elongated so referred as muscle fibers Fleshy • Definition • Muscle is a contractile tissue which brings about movements Tendons Muscle makes up 30-35% (in women) & 40-45% (in men) of body mass Type of muscles BASED ON BASED ON BASED ON LOCATION STRIATIONS CONTROL Skeletal / Somatic STRIATED / STRIPED VOLUNTARY Smooth / Visceral UN-STRIATED / IN-VOLUNTARY UNSTRIPED Cardiac STRIATED / STRIPED IN-VOLUNTARY SKELETAL MUSCLE Skeletal muscle organization Muscles are complex structures: arranged in fascicles Muscle bundles / fascicles • Epimysium surrounds entire muscle – Dense CT that merges with tendon – Epi = outer, Mys = muscle • Perimysium surrounds muscle fascicles – Peri = around – Within a muscle fascicle are many muscle fibers • Endomysium surrounds muscle fiber – Endo = within SKELETAL MUSCLE • Each bundles contains many muscle fiber Structure of a skeletal muscle fiber • Elongated, unbranched cylindrical fibers • Length- 1 mm – 5 cm, Width – 10 mm - 100μm • Fibers have striations of dark & light bands • Many flat nuclei beneath sarcolemma • Plasma membrane = sarcolemma • Smooth endoplsmic reticulum = sarcoplasmic reticulum (SR) • Cytoplasm = sarcoplasm • Mitochondria = sarcosomes • Each muscle fiber made of long cylindrical myofibrils Structure
    [Show full text]
  • Muscle Contraction
    Muscle Physiology Dr. Ebneshahidi © 2009 Ebneshahidi Skeletal Muscle Figure 9.2 (a) © 2009 Ebneshahidi Functions of the muscular system . 1. Locomotion – body movements are due to skeletal muscle contraction. 2. Vasoconstriction and vasodilatation - constriction and dilation of blood vessel walls are the results of smooth muscle contraction. 3. Peristalsis – wavelike motion along the digestive tract is produced by the smooth muscle. 4. Cardiac motion – heart chambers pump blood to the lungs and to the body because of cardiac muscle contraction. 5. Posture maintenance - contraction of skeletal muscles maintains body posture and muscle tone. 6. Heat generation – about 75% of ATP energy used in muscle contraction is released as heat. © 2009 Ebneshahidi Comparison of the three types of muscle . Striation: only present in skeletal and cardiac muscles. Absent in smooth muscle. Nucleus: smooth and cardiac muscles are uninculcated (one nucleus per cell) skeletal muscle is multinucleated (several nuclei per cell). Transverse tubule (T tubule): well developed in skeletal and cardiac muscles to transport calcium. Absent in smooth muscle. Intercalated disk: specialized intercellular junction that only occurs in cardiac muscle. Control: skeletal muscle is always under voluntary control‚ with some exceptions (the tongue and pili arrector muscles in the dermis). Smooth and cardiac muscles are under involuntary control. © 2009 Ebneshahidi Innervation: motor unit . a) a motor nerve and a myofibril from a neuromuscular junction where gap (called synapse) occurs between the two structures. At the end of motor nerve‚ neurotransmitter (i.e. acetylcholine) is stored in synaptic vesicles which will release the neurotransmitter using exocytosis upon the stimulation of a nerve impulse.
    [Show full text]
  • Muscle Tissue[PDF]
    Muscle Tissue BY Dr Navneet Kumar Professor Anatomy KGMU LKO Dr Navneet Kumar Professor Anatomy KGMU LKO Muscle Tissue A muscle tissue is made of contractile cells Dr Navneet Kumar Professor Anatomy KGMU LKO Muscle Tissue • Types- • 1.Muscle tissue -Skeletal muscle -Smooth muscle -Cardiac muscle 2.Single cell unite -myoepithelial cells -myofibroblast cells Dr Navneet Kumar Professor Anatomy KGMU LKO Muscle Tissue Plasma membrane -Sarcolema Cytoplasm -Sarcoplasm Endoplasmic reticulum-Sarcoplasmic reticulum Mitochondria- -Sarcosome Dr Navneet Kumar Professor Anatomy KGMU LKO Skeletal muscle…. • Epi mysium • Peri mysium • Endo mysium Dr Navneet Kumar Professor Anatomy KGMU LKO SKELETAL MUSCLE Dr Navneet Kumar Professor Anatomy KGMU LKO Skeletal muscle • features • Skeletal muscle composed of muscle fibres • Each muscle fibre is an elongated unbranched cell, voluntary • Nuclei present at periphery • Striations, Alternative dark and light bands Dr Navneet Kumar Professor Anatomy KGMU LKO Skeletal muscle….. E.M. Structure • Muscle fibre or Muscle cell A muscle fibre (muscle cell) contains bundle of myofibril Myofibril • myofibrils are made of myofilaments Myofilament -Thick myofilaments- myosin protein -Thin myofilaments- actin protein Cross striations are the result of overlapping of myosin protein& actin protein - Transvers tubule system - triad Dr Navneet Kumar Professor Anatomy KGMU LKO Arrangement of myofibril Dr Navneet Kumar Professor Anatomy KGMU LKO Dr Navneet Kumar Professor Anatomy KGMU LKO Arrangement of Myofilament -Dark band-’A’
    [Show full text]
  • The Linker of Des-Glu84-Calmodulin Is Bent (Calcium/Mutagenesis/Flexible Tether/Bent A-Helix/Crystallography) S
    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 6869-6873, July 1993 Biochemistry The linker of des-Glu84-calmodulin is bent (calcium/mutagenesis/flexible tether/bent a-helix/crystallography) S. RAGHUNATHAN*, R. J. CHANDROSSt, B.-P. CHENG*t, A. PERSECHINI*§, S. E. SOBOTTKAt, AND R. H. KRETSINGER* Departments of *Biology and tPhysics, University of Virginia, Charlottesville, VA 22901 Communicated by William N. Lipscomb, April 1, 1993 ABSTRACT The crystal structure of a mutant calmodulin 111111111122 22222222 (CaM) lacking Glu-84 has been refined to R = 0.23 using data 123456789 012345678901 23456789 measured to 2.9-A resolution. In native CaM the central helix domain n nn n X Y Z(Y) X Z n nn n is fully extended, and the molecule is dumbbell shaped. In contrast, the deletion of Glu-84 causes a bend of 950 in the 1 ADQLTEEQIA EFKEAFSLF DKDGDGTITTKE LGTVMRSL39 linker region of the central helix at Ile-85. However, EF-hand 2 GQNPTEA ELQDMINEV DADGNGTIDrPz rLTMKARKP75 domains 1 and 2 (lobe 1,2) do not touch lobe 3,4. The length, by a-carbon separation, of des-Glu5"-CaM is 56 A; that of 3 76MKDTDSEE EIRZAFRVr DKDGNGYISAAE LRHVMTNL112 native CaM is 64 A. The shape of des-Glu"-CaM is similar to 4 GEKLTDE EVDEMIREA DIDGDGQVNYEE FVQMMTAK148 that ofnative CaM, as it is bound to the target peptide ofmyosin light-chain kinase. This result supports the proposal that the FIG. 1. The amino acid sequence ofvertebrate CaM is aligned by linker region of the central helix of CaM functions as a flexible its four EF-hand domains, each consisting of 29 residues.
    [Show full text]
  • Muscle Tissue and Organization 289
    MUSCULAR SYSTEM OUTLINE 10.1 Properties of Muscle Tissue 289 10.2 Characteristics of Skeletal Muscle Tissue 289 10 10.2a Functions of Skeletal Muscle Tissue 289 10.2b Gross Anatomy of Skeletal Muscle 290 10.2c Microscopic Anatomy of Skeletal Muscle 293 10.3 Contraction of Skeletal Muscle Fibers 298 Muscle 10.3a The Sliding Filament Theory 298 10.3b Neuromuscular Junctions 298 10.3c Physiology of Muscle Contraction 301 10.3d Muscle Contraction: A Summary 303 Tissue and 10.3e Motor Units 303 10.4 Types of Skeletal Muscle Fibers 305 10.4a Distribution of Slow, Intermediate, and Fast Fibers 307 10.5 Skeletal Muscle Fiber Organization 307 Organization 10.5a Circular Muscles 307 10.5b Parallel Muscles 307 10.5c Convergent Muscles 307 10.5d Pennate Muscles 307 10.6 Exercise and Skeletal Muscle 309 10.6a Muscle Atrophy 309 10.6b Muscle Hypertrophy 309 10.7 Levers and Joint Biomechanics 309 10.7a Classes of Levers 309 10.7b Actions of Skeletal Muscles 310 10.8 The Naming of Skeletal Muscles 311 10.9 Characteristics of Cardiac and Smooth Muscle 312 10.9a Cardiac Muscle 312 10.9b Smooth Muscle 313 10.10 Aging and the Muscular System 313 10.11 Development of the Muscular System 317 MODULE 6: MUSCULAR SYSTEM mck78097_ch10_288-321.indd 288 2/14/11 3:42 PM Chapter Ten Muscle Tissue and Organization 289 hen most of us hear the word “muscle,” we think of the W muscles that move the skeleton. These muscles are con- 10.2 Characteristics of Skeletal sidered organs because they are composed not only of muscle Muscle Tissue tissue, but also of epithelial, connective, and nervous tissue.
    [Show full text]
  • Levels of Muscle Structure
    Levels of Muscle Structure • Muscle • Muscle Bundle • Muscle Fiber (myofiber) • Myofibrils • Myofilaments 1 Muscle Muscle Bundle • Contains 10-20 myofibers • Encased by perimysium • Can see with the naked eye Myofiber (Muscle fiber) • Individual muscle cell • Multinucleated • Encased by endomysium • Cell wall: sarcolemma 2 Myofibrils • Embedded in sarcoplasm • Mitochondria located between myofibrils Myofibrils • Comprised of repeating units: sarcomeres – A band – I band –Z disk –H zone – Pseudo-H zone 3 Sarcomere Sarcomere Myofilaments • Contractile Proteins – Myosin – Actin • Regulatory Proteins – Tropomyosin – Troponin • Structural Proteins – Z – Line Proteins 4 Contractile Proteins • Myosin – 70 – 80% of the total protein – Thick filament – Burns the ATP for muscle contraction Myosin & Its Fragments Chymotrypsin – Myosin head moves S1 back and forth to perform a muscle ROD Alkali Reg ula to r y li g ht c h ain - light chain COO contraction LMM COO- Actin binding and A TPa se activity HMM Trypsin Contractile Proteins • Actin – 20% of the myofibrillar protein – Thin Filament – Globular protein (G- protein) – Arranged like a twisted pearl necklace (F-protein) – Myosin head attaches to the Actin Regulatory Proteins • Regulate contraction and the speed of contraction • Tropomyosin • Troponin 5 Regulatory Proteins • Tropomyosin – Thin protein that lays around the Actin proteins AA End View Top View Regulatory Proteins • Troponin • 3 Subunits – TnT • Binds tropomyosin – TnI • Inhibitory subunit – TnC • Ca2+ binding subunit 3 Dimensional 6
    [Show full text]
  • Skletal Muscle Tissue
    SKELETAL MUSCLE Site • All skeletal muscle attached to skeleton. • Tongue. • Larynx. • Pharynx. • Eye. Types: – Striated Voluntary (under control of will) except:- – upper third of esophagus. – pharynx. – cremasteric muscle. • Do not branch Except:- – tongue and face. Structure of SK. M.: • It is formed of cells (fibers) and connective tissue. A. Connective tissue: 1-Epimysium • It is a dense C.T. which surround the whole muscle. 2-Perimysium • It is a dense C.T. which divides the muscle into bundles (each bundle contain a group of muscle fibers). 3-Endomysium: • It is a loose C.T. which separates the muscle fibers. Function of C.T.: • 1-It contains blood vessels, nerves and lymphatic. • 2-Give attachment between muscle bundles. • 3-Help the attachment of muscle to tendon, ligament, perichondrium and periostium. B- Skeletal Muscle F.: L/M of Sk. M. Fiber: T/S: -Polyhedral in shape. -100 um in diameter. -The nucleus is only seen in some fibers. -The sarcoplasm may show dark areas (Cohnheim's areas) due to grouping of the myofibrils. L/S: • Single elongated mutinucleated cell (syncytium). • 1-40 mm. in length. • 10-100 um in diameter. • Have multiple flattened oval peripherally situated nuclei. • Have regular transverse striation. • The sarcoplasm is acidophilic and contains: • B- Glycogen granules. • Myoglobin pigment. E/M of Skeletal Muscle Fiber: • The sarcoplasm show tubular envaginations (T.T.). • Plenty of mitochondria. • Smooth endoplasmic reticulum (arcoplasmic reticulum). • Ribosomes. • B- Glycogen granules. • Myoglobin pigment. • Myofibrils (sarcostyles) (Actin &Myosin F.) Myofibrils (Sarcostyles) Definition: • These are contractile elements which are longitudinally arranged in the sarcoplasm of the skeletal muscle fiber.
    [Show full text]
  • Cell Death, Clearance and Immunity in the Skeletal Muscle
    Cell Death and Differentiation (2016) 23, 927–937 & 2016 Macmillan Publishers Limited All rights reserved 1350-9047/16 www.nature.com/cdd Review Cell death, clearance and immunity in the skeletal muscle C Sciorati1, E Rigamonti1, AA Manfredi1,2 and P Rovere-Querini*,1,2 The skeletal muscle is an immunologically unique tissue. Leukocytes, virtually absent in physiological conditions, are quickly recruited into the tissue upon injury and persist during regeneration. Apoptosis, necrosis and autophagy coexist in the injured/ regenerating muscles, including those of patients with neuromuscular disorders, such as inflammatory myopathies, dystrophies, metabolic and mitochondrial myopathies and drug-induced myopathies. Macrophages are able to alter their function in response to microenvironment conditions and as a consequence coordinate changes within the tissue from the early injury throughout regeneration and eventual healing, and regulate the activation and the function of stem cells. Early after injury, classically activated macrophages (‘M1’) dominate the picture. Alternatively activated M2 macrophages predominate during resolution phases and regulate the termination of the inflammatory responses. The dynamic M1/M2 transition is increasingly felt to be the key to the homeostasis of the muscle. Recognition and clearance of debris originating from damaged myofibers and from dying stem/ progenitor cells, stromal cells and leukocytes are fundamental actions of macrophages. Clearance of apoptotic cells and M1/M2 transition are causally connected and represent limiting steps for muscle healing. The accumulation of apoptotic cells, which reflects their defective clearance, has been demonstrated in various tissues to prompt autoimmunity against intracellular autoantigens. In the muscle, in the presence of type I interferon, apoptotic myoblasts indeed cause the production of autoantibodies, lymphocyte infiltration and continuous cycles of muscle injury and regeneration, mimicking human inflammatory myopathies.
    [Show full text]