Role of Sarcoendoplasmic Reticulum Calcium ATPase Pump in Airway Smooth Muscle Function
Role of Sarcoendoplasmic Reticulum Calcium ATPase Pump in Airway Smooth Muscle Function

Author: Oluwaseun O Ojo

Publisher:

Published: 2011

Total Pages: 398

ISBN-13:

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Asthma is a chronic inflammatory disease of the airway with hallmarks of remodelling, inflammation, hyper-responsiveness and bronchonstricition. All of these implicate airway smooth muscle (ASM) and alterations in ASM calcium homeostasis. We have found that the latter is mediated through diminished SERCA-2 expression, which correlates with disease severity. I investigated the role of SERCA-2 knock-down on ASM function using siRNA in ASM cells from healthy volunteers, and studied responses implicated in airway remodelling and inflammation. Calcium transients in healthy ASM following SERCA-2 knock-down resembled those from asthmatic ASM. Likewise, ASM proliferation in response to FBS and PDGF-[beta][beta], estimated using 3H-thymidine incorporation, was increased following SERCA-2 knock-down, similar to untreated ASM cells from asthmatics. SERCA-2 knock-down in both healthy and asthmatic ASM cells also elicited an increase in eotaxin-1 production in both untreated and IL-13 treated ASM cells. Collectively these data strongly suggest a key role for reduced SERCA-2 expression in the altered function and phenotype of ASM from asthmatics. To identify the cause of the diminished expression of SERCA-2 in asthma, I investigated the effect of asthma-associated mediators (cytokines and therapy) on SERCA-2 expression in healthy ASM cells, and observed decreased SERCA-2 expression following treatment with IL-13 and transforming growth factor- [beta](TGF[beta]); the later caused a reduction in expression that was sustained up to 14 days after removal of TGF[beta] following an initial 24 and 72 hrs exposure. Similarly, the long acting [beta]2 adrenoreceptor agonist formoterol also caused reduced expression of SERCA-2, and this was prevented by [beta]2 antagonists (ICI-118551) and inhibition of ERK signalling.

Role of the Sarcoplasmic Reticulum in Smooth Muscle
Role of the Sarcoplasmic Reticulum in Smooth Muscle

Author: Derek J. Chadwick

Publisher: John Wiley & Sons

Published: 2003-07-07

Total Pages: 296

ISBN-13: 0470852933

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Smooth muscle contraction is a vital component of the functioning of blood vessels, the uterus, airways and the bladder. Its malfunction can lead to serious pathological conditions, such as hypertension and pre-term labour. The calcium ion plays a central role in smooth muscle function, increasing in concentration for contraction and decreasing for relaxation. Calcium entry into the cell is facilitated by the sarcoplasmic reticulum (SR). This book explores the latest research on the role of the sarcoplasmic reticulum (SR) in smooth muscle function. It examines the control and modulation of the SR and how this may vary among smooth muscle types. Potential therapeutic implications are also discussed. Discusses new and exciting work in this area and identifies promising new research directions. Considers the advances in this relatively unexplored field, offering new insights into the role of the SR muscle. Brings together contributions from key workers, both in basic and clinical science, whose studies range from physiological to pathological and molecular to whole animal.

Cellular Aspects of Smooth Muscle Function
Cellular Aspects of Smooth Muscle Function

Author: C. Y. Kao

Publisher: Cambridge University Press

Published: 1997-08-28

Total Pages: 324

ISBN-13: 9780521482103

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Smooth muscles line many internal organs and, in general, are involved in moving fluids and slurry around the body. They are controlled by the action of hormones, by nervous stimulation, and can be influenced by drugs. This 1997 book provides a review of our understanding of smooth muscle and integrates molecular, cellular and physiological information with tissue and anatomical studies. Well-known researchers have written chapters giving detailed reviews of our current knowledge of the biochemistry, pharmacology, physiology and anatomy of smooth muscle. In particular, they cover the seven most important areas of smooth muscle function including morphology, electrophysiology, mechanisms of electromechanical and pharmacomechanical coupling, calcium homeostasis, signal transduction, mechanics of contraction, and the contractile proteins. All those interested in muscular contraction will find this book worthwhile, whether they are biochemists, physiologists, or cell biologists.

Regulation of Vascular Smooth Muscle Function
Regulation of Vascular Smooth Muscle Function

Author: Raouf A. Khalil

Publisher: Biota Publishing

Published: 2010-05-01

Total Pages: 78

ISBN-13: 1615041818

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Vascular smooth muscle (VSM) constitutes most of the tunica media in blood vessels and plays an important role in the control of vascular tone. Ca2+ is a major regulator of VSM contraction and is strictly regulated by an intricate system of Ca2+ mobilization and Ca2+ homeostatic mechanisms. The interaction of a physiological agonist with its plasma membrane receptor stimulates the hydrolysis of membrane phospholipids and increases the generation of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 stimulates Ca2+ release from the intracellular stores in the sarcoplasmic reticulum. Agonists also stimulate Ca2+ influx from the extracellular space via voltage-gated, receptor-operated, and store-operated channels. Ca2+ homeostatic mechanisms tend to decrease the intracellular free Ca2+ concentration ([Ca2+]i) by activating Ca2+ extrusion via the plasmalemmal Ca2+ pump and the Na+/Ca2+ exchanger and the uptake of excess Ca2+ by the sarcoplasmic reticulum and possibly the mitochondria. A threshold increase in [Ca2+]i activates Ca2+-dependent myosin light chain (MLC) phosphorylation, stimulates actin–myosin interaction, and initiates VSM contraction. The agonist-induced maintained increase in DAG also activates specific protein kinase C (PKC) isoforms, which in turn cause phosphorylation of cytoplasmic substrates that increase the contractile myofilaments force sensitivity to Ca2+ and thereby enhance VSM contraction. Agonists could also activate Rho kinase (ROCK), leading to inhibition of MLC phosphatase and further enhancement of the myofilaments force sensitivity to Ca2+. The combined increases in [Ca2+]i, PKC and ROCK activity cause significant vasoconstriction and could also stimulate VSM hypertrophy and hyperplasia. The protracted and progressive activation of these processes could lead to pathological vascular remodeling and vascular disease.

Regulation of Smooth Muscle Contraction
Regulation of Smooth Muscle Contraction

Author: Robert S. Moreland

Publisher: Springer Science & Business Media

Published: 2012-12-06

Total Pages: 547

ISBN-13: 146846003X

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Sixth Annual Graduate Hospital Research Symposium REGULATION OF SMOOTH MUSCLE PROGRESS IN SOLVING THE PUZZLE Every so often a scientific conference comes at a time when everyone has new and exciting information, when old "dogmas" do not seem to be as well established, and when speakers and participants alike are ready to challenge interpretations of old and new experimental data. This was such a conference. What turns on a smooth muscle cell? The precise answer to this question has eluded scientists for much longer than I have been involved in the field. We know that an increase in cytosolic calcium is necessary and we know that phosphorylation of the 20 kDa myosin light chain is an important step in the process. We do not know if other processes are necessary for the initiation and lor maintenance of a smooth muscle contraction nor do we know if other processes modulate the regulation of contraction. The goal of the symposium on which this volume is based was to explore the most current hypotheses for the answers to these questions. I believe that after reading the chapters included in this volume, you will agree that this goal was achieved. The importance of calcium and calmodulin dependent myosin light chain phosphoryla tion in the regulation of smooth muscle contraction was reinforced by many presentations. However, the status of myosin light chain phosphorylation as a simple calcium dependent switch came under serious suspicion.

Calcium in Muscle Activation
Calcium in Muscle Activation

Author: Johann C. Rüegg

Publisher: Springer Science & Business Media

Published: 2012-12-06

Total Pages: 309

ISBN-13: 364296981X

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This book offers a comparative and interdisciplinary approach to excitation-contraction-coupling in smooth and striated mus cles, including the myocardium. It is an account of the path ways and mechanisms by which cellular calcium is handled and activates the contractile proteins. It also describes how these mechanisms are adapted in various kinds of muscle to meet specific functional requirements, such as speed or economy. This monograph then presents facts, ideas and theories and the evidence on which they are based, and ifit stimulates others and furthers research, it will have served its purpose. All of the chapters are self-contained and may be read in any order, but readers unfamiliar with muscle are recommended to start with the introductory chapter on excitation and contraction. During all the years of writing this book, I received enormous help from Isolde Berger who corrected, edited and transformed my innumerable notes and drafts into a readable manuscript; she also compiled the list of references and the Subject Index. I owe a great debt of gratitude to her and also to Claudia Zeugner, who prepared the figures with expertise and care. Then I would like to thank the Deutsche F orschungs gemeinschaft and the Fritz-Thyssen-Stiftung for supporting the work of my Department which has been reported in this monograph. A great many people contributed with helpful discussions.

Calcium and Contractility
Calcium and Contractility

Author: A. K. Grover

Publisher: Springer Science & Business Media

Published: 2012-12-06

Total Pages: 498

ISBN-13: 1461251729

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In organizing the present volume, we had two intentions. The first was to present the best current understanding of the mechanisms of calcium mobilization during excitation contraction coupling of smooth muscle at a level suited to the needs of professionals interested in smooth muscle pharmacology and pathophysiology, while remaining appreciable by graduate and medical students. The second intention was to provide in sight into present-day controversies, as well as the latest ad vances achieved by researchers in this field. Thus, we have thor oughly discussed both the techniques and the concepts derived from their application. An attempt has also been made here to answer a number of profoundly important questions: What are the mechanisms and agents responsible for the control of contractility? What are the accompanying changes in the state of intracellular calcium ions and the mechanisms responsible for them? How does the regula tion of contractility occur directly at the level of the actomyosin activity? What role do gap junctions play in cell-to-cell coupling? What are the roles of cholinergic, adrenergic, peptidergic, and nonadrenergic noncholinergic interactions in calcium mobiliza tion in smooth muscle? What changes occur in hypertension? The impact of these recent techniques on future research is also reflected upon.

The Development of the Sarcoplasmic Reticulum
The Development of the Sarcoplasmic Reticulum

Author: Anthony Martonosi

Publisher: CRC Press

Published: 2003-09-02

Total Pages: 707

ISBN-13: 0203305019

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Sarcoplasmic reticulum is a form of endoplasmic reticulum found in large quantities in mature muscle cells. Anthony Martonosi presents general information about the development and function of the sarcoplasmic reticulum within a framework of contemporary research on the molecular biology of biosynthetic and signaling processes. Focusing on the development of the sarcoplasmic reticulum, Martonosi demonstrates the regulatory functions that control the production of its molecular components and investigates the interaction of these lipid and protein molecules with the myogenic, neurogenic and hormonal stimuli present in developing muscle cells. Martonosi provides extensive experimental support throughout the book.