The Connection Between Actin Atpase and Polymerization
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Appropriate Roles of Cardiac Troponins in Evaluating Patients with Chest Pain
J Am Board Fam Pract: first published as 10.3122/jabfm.12.3.214 on 1 May 1999. Downloaded from MEDICAL PRACTICE Appropriate Roles of Cardiac Troponins in Evaluating Patients With Chest Pain Matthew S. Rice, MD, CPT, Me, USA, and David C. MacDonald, DO, Me, USA Background: Diagnosis of acute myocardial infarction relies upon the clinical history, interpretation of the electrocardiogram, and measurement of serum levels of cardiac enzymes. Newer biochemical markers of myocardial injury, such as cardiac troponin I and cardiac troponin T, are now being used instead of or along with the standard markers, the MB isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase. Methods: We performed a MEDLINE literature search (1987 to 1997) using the key words "troponin I," "troponin T," and "acute myocardial infarction." We reviewed selected articles related to the diagnostic and prognostic usefulness of these cardiac markers in evaluating patients with suspected myocardial infarction. Results: We found that (1) troponin I is a better cardiac marker than CK-MB for myocardial infarction because it is equally sensitive yet more specific for myocardial injury; (2) troponin T is a relatively poorer cardiac marker than CK-MB because it is less sensitive and less specific for myocardial injury; and (3) both troponin I and troponin T may be used as independent prognosticators of future cardiac events. Conclusions: Troponin I is a sensitive and specific marker for myocardial injury and can be used to predict the likelihood of future cardiac events. It is not much more expensive to measure than CK-MB. Over all, troponin I is a better cardiac marker than CK-MB and should become the preferred cardiac enzyme when evaluating patients with suspected myocardial infarction. -
Familial Adenomatous Polyposis Polymnia Galiatsatos, M.D., F.R.C.P.(C),1 and William D
American Journal of Gastroenterology ISSN 0002-9270 C 2006 by Am. Coll. of Gastroenterology doi: 10.1111/j.1572-0241.2006.00375.x Published by Blackwell Publishing CME Familial Adenomatous Polyposis Polymnia Galiatsatos, M.D., F.R.C.P.(C),1 and William D. Foulkes, M.B., Ph.D.2 1Division of Gastroenterology, Department of Medicine, The Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada, and 2Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada Familial adenomatous polyposis (FAP) is an autosomal-dominant colorectal cancer syndrome, caused by a germline mutation in the adenomatous polyposis coli (APC) gene, on chromosome 5q21. It is characterized by hundreds of adenomatous colorectal polyps, with an almost inevitable progression to colorectal cancer at an average age of 35 to 40 yr. Associated features include upper gastrointestinal tract polyps, congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, and other extracolonic malignancies. Gardner syndrome is more of a historical subdivision of FAP, characterized by osteomas, dental anomalies, epidermal cysts, and soft tissue tumors. Other specified variants include Turcot syndrome (associated with central nervous system malignancies) and hereditary desmoid disease. Several genotype–phenotype correlations have been observed. Attenuated FAP is a phenotypically distinct entity, presenting with fewer than 100 adenomas. Multiple colorectal adenomas can also be caused by mutations in the human MutY homologue (MYH) gene, in an autosomal recessive condition referred to as MYH associated polyposis (MAP). Endoscopic screening of FAP probands and relatives is advocated as early as the ages of 10–12 yr, with the objective of reducing the occurrence of colorectal cancer. -
ATP and Cellular Work | Principles of Biology from Nature Education
contents Principles of Biology 23 ATP and Cellular Work ATP provides the energy that powers cells. Magnetic resonance images of three different areas in the rat brain show blood flow and the biochemical measurements of ATP, pH, and glucose, which are all measures of energy use and production in brain tissue. The image is color-coded to show spatial differences in the concentration of these energy-related variables in brain tissue. © 1997 Nature Publishing Group Hoehn-Berlage, M., et al. Inhibition of nonselective cation channels reduces focal ischemic injury of rat brain. Journal of Cerebral Blood Flow and Metabolism 17, 534–542 (1997) doi: 10.1097/00004647-199705000-00007. Used with permission. Topics Covered in this Module Using Energy Resources For Work ATP-Driven Work Major Objectives of this Module Describe the role of ATP in energy-coupling reactions. Explain how ATP hydrolysis performs cellular work. Recognize chemical reactions that require ATP hydrolysis. page 116 of 989 4 pages left in this module contents Principles of Biology 23 ATP and Cellular Work Energy is a fundamental necessity for all of life's processes. Without energy, flagella cannot move, DNA cannot be unwound or separated for replication or gene expression, cells cannot divide, plants cannot grow and animals cannot reproduce. Energy is vital, but where does it come from? Plants and photosynthetic microbes capture light energy and convert it into chemical energy for their own use. Organisms that cannot produce their own food, such as fungi and animals, feed upon this captured energy. However, the chemical energy produced by photosynthesizers needs to be converted into a usable form. -
Alpha-Actinin-3 R577X
Annals of Applied Sport Science, vol. 4, no. 4, pp. 01-06, Winter 2016 DOI: 10.18869/acadpub.aassjournal.4.4.1 Short Communication www.aassjournal.com www.AESAsport.com ISSN (Online): 2322 – 4479 Received: 20/03/2016 ISSN (Print): 2476–4981 Accepted: 10/06/2016 Alpha-actinin-3 R577X Polymorphism Profile of Turkish Professional Hip-Hop and Latin Dancers 1,2 * 1 1 2 1 1 Korkut Ulucan , Betul Biyik, Sezgin Kapici, Canan Sercan, Oznur Yilmaz, Tunc Catal 1Üsküdar Univerity, Haluk Turksoy Sok. No:14, Altunizade, Üsküdar, İstanbul, Turkey. 2Marmara University, BAsibuyuk Yolu 9/3 MAltepe Saglık Yerleşkesi, MAltepe, Istanbul, Turkey. ABSTRACT Actins are small globular filaments functioning in cell processes like muscle contraction, and stabilized to the sarcomeric Z- discs by actin binding proteins (actinins). One of the important gene coding for actin binding proteins in fast twitch fibers is alpha- actinin- 3 (ACTN3). In this research, we have conducted a gene profile study investigating the genotype and allele distributions of ACTN3 R577X polymorphism in Turkish professional hip- hop and latin dancers and compared them to non-dancers as a control group. 30 professional dancers and non-dancers were recruited for the study. A genotyping procedure was carried out by a newly introduced four-primer PCR methodology. For statistical analysis, the Chi-square test was used to compare data between the groups (p<0,05 evaluated as significant). Numbers and the percentages of dancers were 2 (7%), 21 (70%) and 7(23%) for RR, RX and XX genotypes, respectively. The same numbers and the percentages were 15 (50%), 8 (15%) and 7 (23%) for RR, RX and XX genotypes, respectively, for the controls. -
Troponin Variants in Congenital Myopathies: How They Affect Skeletal Muscle Mechanics
International Journal of Molecular Sciences Review Troponin Variants in Congenital Myopathies: How They Affect Skeletal Muscle Mechanics Martijn van de Locht , Tamara C. Borsboom, Josine M. Winter and Coen A. C. Ottenheijm * Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Location VUmc, 1081 HZ Amsterdam, The Netherlands; [email protected] (M.v.d.L.); [email protected] (T.C.B.); [email protected] (J.M.W.) * Correspondence: [email protected]; Tel.: +31-(0)-20-444-8123 Abstract: The troponin complex is a key regulator of muscle contraction. Multiple variants in skeletal troponin encoding genes result in congenital myopathies. TNNC2 has been implicated in a novel congenital myopathy, TNNI2 and TNNT3 in distal arthrogryposis (DA), and TNNT1 and TNNT3 in nemaline myopathy (NEM). Variants in skeletal troponin encoding genes compromise sarcomere function, e.g., by altering the Ca2+ sensitivity of force or by inducing atrophy. Several potential therapeutic strategies are available to counter the effects of variants, such as troponin activators, introduction of wild-type protein through AAV gene therapy, and myosin modulation to improve muscle contraction. The mechanisms underlying the pathophysiological effects of the variants in skeletal troponin encoding genes are incompletely understood. Furthermore, limited knowledge is available on the structure of skeletal troponin. This review focusses on the physiology of slow and fast skeletal troponin and the pathophysiology of reported variants in skeletal troponin encoding genes. A better understanding of the pathophysiological effects of these variants, together with enhanced knowledge regarding the structure of slow and fast skeletal troponin, will direct the development of Citation: van de Locht, M.; treatment strategies. -
Actin-Troponin-Tropomyosin Complex (Muscle Relaxation/Cooperativity/Regulated Actin) Lois E
Proc. Nati. Acad. Sci. USA Vol. 77, No. 5, pp. 2616-2620, May 1980 Biochemistry Cooperative binding of myosin subfragment-1 to the actin-troponin-tropomyosin complex (muscle relaxation/cooperativity/regulated actin) Lois E. GREENE AND EVAN EISENBERG Laboratory of Cell Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20205 Communicated by Terrell L. Hill, February 22, 1980 ABSTRACT The binding of myosin subfragment-1 (S-i) to of a few S-1 molecules, free of ATP, to the actin filament and the F-actin-troponin-tropomyosin complex (regulated F-actin). pushing the tropomyosin away from its inhibitory position, thus was examined in the presence of ADP (ionic strength, 0.23 M; preventing inhibition of the ATPase activity even in the absence 220C) by using the ultracentrifuge and S-1 blocked at SHI with iodo["4C]acetamide. S-1ADP binds with positive cooperativity of Ca2+. Cooperative responses have also been observed in the to regulated F-actin, both in the presence and absence of cal- presence of Ca2+. Weber and coworkers (6) found that at high cium; it binds independently to unregulated actin. With and S-1 concentration the ATPase activity of regulated acto-S-1 can without CaO+ at very low levels of occupancy of the regulated be potentiated so that it is higher than the ATPase activity of actin by S-19ADP, S-1*ADP binds to the regulated actin with acto*S-1 in the absence of troponin-tropomyosin. <1% of the strength that it binds to unregulated actin, whereas The cooperative responses observed with regulated actin are at high levels of occupancy of the regulated actin by S-1-ADP, S-1ADP binds about 3-fold more strongly to the regulated actin fundamental to our understanding of the biochemical basis of than it does to unregulated actin. -
Α-Actinin/Titin Interaction: a Dynamic and Mechanically Stable Cluster of Bonds in the Muscle Z-Disk
α-Actinin/titin interaction: A dynamic and mechanically stable cluster of bonds in the muscle Z-disk Marco Grisona, Ulrich Merkela, Julius Kostanb, Kristina Djinovic-Carugob,c, and Matthias Riefa,d,1 aPhysik Department E22, Technische Universität München, 85748 Garching, Germany; bDepartment of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria; cDepartment of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 Ljubljana, Slovenia; and dMunich Center for Integrated Protein Science, 81377 Munich, Germany Edited by James A. Spudich, Stanford University School of Medicine, Stanford, CA, and approved December 16, 2016 (received for review August 2, 2016) Stable anchoring of titin within the muscle Z-disk is essential for In humans, the isoforms of titin exhibit four to seven Z-repeats preserving muscle integrity during passive stretching. One of the (15, 16, 20). The structure of the EF3-4 hands complex with titin main candidates for anchoring titin in the Z-disk is the actin cross- Z-repeat 7 shows the bound Z-repeat in an α-helical confor- linker α-actinin. The calmodulin-like domain of α-actinin binds to mation (21). In solution assays, binding affinities of various the Z-repeats of titin. However, the mechanical and kinetic prop- Z-repeats to EF3-4 were determined to lie in the micromolar erties of this important interaction are still unknown. Here, we use range (22). Micromolar affinity points only to a moderately a dual-beam optical tweezers assay to study the mechanics of this stable interaction, the kinetics of which are unknown. -
Current Understanding of the Role of Cytoskeletal Cross-Linkers in the Onset and Development of Cardiomyopathies
International Journal of Molecular Sciences Review Current Understanding of the Role of Cytoskeletal Cross-Linkers in the Onset and Development of Cardiomyopathies Ilaria Pecorari 1, Luisa Mestroni 2 and Orfeo Sbaizero 1,* 1 Department of Engineering and Architecture, University of Trieste, 34127 Trieste, Italy; [email protected] 2 University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; [email protected] * Correspondence: [email protected]; Tel.: +39-040-5583770 Received: 15 July 2020; Accepted: 10 August 2020; Published: 15 August 2020 Abstract: Cardiomyopathies affect individuals worldwide, without regard to age, sex and ethnicity and are associated with significant morbidity and mortality. Inherited cardiomyopathies account for a relevant part of these conditions. Although progresses have been made over the years, early diagnosis and curative therapies are still challenging. Understanding the events occurring in normal and diseased cardiac cells is crucial, as they are important determinants of overall heart function. Besides chemical and molecular events, there are also structural and mechanical phenomena that require to be investigated. Cell structure and mechanics largely depend from the cytoskeleton, which is composed by filamentous proteins that can be cross-linked via accessory proteins. Alpha-actinin 2 (ACTN2), filamin C (FLNC) and dystrophin are three major actin cross-linkers that extensively contribute to the regulation of cell structure and mechanics. Hereby, we review the current understanding of the roles played by ACTN2, FLNC and dystrophin in the onset and progress of inherited cardiomyopathies. With our work, we aim to set the stage for new approaches to study the cardiomyopathies, which might reveal new therapeutic targets and broaden the panel of genes to be screened. -
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. -
Structural Insight Into Signal Conversion and Inactivation by Ntpdase2 in Purinergic Signaling
Structural insight into signal conversion and inactivation by NTPDase2 in purinergic signaling Matthias Zebisch and Norbert Stra¨ ter* Center for Biotechnology and Biomedicine, Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany Communicated by William N. Lipscomb, Harvard University, Cambridge, MA, March 13, 2008 (received for review January 4, 2008) Cell surface-located nucleoside triphosphate diphosphohydrolases prominent DXG motif and correspond to the - and ␥-phos- (NTPDase1, -2, -3, and -8) are oligomeric integral membrane pro- phate binding loops of soluble members of the actin/hsp70/sugar teins responsible for signal conversion and inactivation in extra- kinase superfamily (17). cellular nucleotide-mediated ‘‘purinergic’’ signaling. They catalyze NTPDases differ significantly in product formation. This is of the sequential hydrolysis of the signaling molecule ATP via ADP to considerable relevance for the regulation of nucleotide signaling. AMP. Here we present the structure of the extracellular domain of NTPDase1, which corresponds to the lymphoid cell activation Rattus norvegicus NTPDase2 in an active state at resolutions antigen CD39, hydrolyzes ATP processively to AMP [i.e., without between 1.7 Å and 2.1 Å in four different forms: (i) apo form, (ii) release of the intermediate ADP from the active site (18, 19)]. The ternary complex with the nonhydrolyzable ATP analog AMPPNP ectoenzyme is expressed by cells of the immune system, quiescent and cofactor Ca2؉,(iii) quaternary complex with Ca2؉ and bound endothelial cells, vascular smooth muscle cells, and others. Because products AMP and phosphate, and (iv) binary product complex of its ability to hydrolyze both ATP and the platelet activator ADP with AMP only. -
Alpha-Actinin Binding Kinetics Modulate Cellular Dynamics And
Alpha-actinin binding kinetics modulate cellular SEE COMMENTARY dynamics and force generation Allen J. Ehrlichera,b,c,1, Ramaswamy Krishnand, Ming Guob, Cécile M. Bidand, David A. Weitzb, and Martin R. Pollaka,1 aDivision of Nephrology, Department of Medicine, and dDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; bSchool of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; and cDepartment of Bioengineering, McGill University, Montreal, QC, Canada H3A0C3 Contributed by Martin R. Pollak, March 25, 2015 (sent for review January 14, 2015) The actin cytoskeleton is a key element of cell structure and homology regions, which together create actin-binding domains movement whose properties are determined by a host of accessory (ABDs). These domains on opposite ends of the dimer allow proteins. Actin cross-linking proteins create a connected network α-actinin to act as a cross-linker, forming networks of loose from individual actin filaments, and though the mechanical effects bundles of actin filaments (11, 12). In humans, there are four of cross-linker binding affinity on actin networks have been in- genes that encode highly homologous forms of α-actinin. Point vestigated in reconstituted systems, their impact on cellular forces is mutations in the ABD of ACTN4 cause a form of kidney damage unknown. Here we show that the binding affinity of the actin cross- known as focal segmental glomerulosclerosis (FSGS) (13–15). linker α-actinin 4 (ACTN4) in cells modulates cytoplasmic mobility, With FSGS, the specialized podocyte cells that form part of the cellular movement, and traction forces. Using fluorescence recovery filtration barrier between the blood and urine lose their normal after photobleaching, we show that an ACTN4 mutation that causes extended structure (13). -
Actin-Titin Interaction in Cardiac Myofibrils: Probing a Physiological Role
Biophysical Journal Volume 73 August 1997 905-919 905 Actin-Titin Interaction in Cardiac Myofibrils: Probing a Physiological Role Wolfgang A. Linke,* Marc lvemeyer,* Siegfried Labeit,# Horst Hinssen,§ J. Caspar Ruegg,* and Mathias Gautel# *Institute of Physiology II, University of Heidelberg, D-69120 Heidelberg; #European Molecular Biology Laboratory, D-69012 Heidelberg; and §Biochemical Cell Biology Group, University of Bielefeld, D-33501 Bielefeld, Germany ABSTRACT The high stiffness of relaxed cardiac myofibrils is explainable mainly by the expression of a short-length titin (connectin), the giant elastic protein of the vertebrate myofibrillar cytoskeleton. However, additional molecular features could account for this high stiffness, such as interaction between titin and actin, which has previously been reported in vitro. To probe this finding for a possible physiological significance, isolated myofibrils from rat heart were subjected to selective removal of actin filaments by a calcium-independent gelsolin fragment, and the "passive" stiffness of the specimens was recorded. Upon actin extraction, stiffness decreased by nearly 60%, and to a similar degree after high-salt extraction of thick filaments. Thus actin-titin association indeed contributes to the stiffness of resting cardiac muscle. To identify possible sites of association, we employed a combination of different techniques. Immunofluorescence microscopy revealed that actin extraction increased the extensibility of the previously stiff Z-disc-flanking titin region. Actin-titin interaction within this region was confirmed in in vitro cosedimentation assays, in which multimodule recombinant titin fragments were tested for their ability to interact with F-actin. By contrast, such assays showed no actin-titin-binding propensity for sarcomeric regions outside the Z-disc comb.