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Mitochondrial Metabolism In Cardiac Ischemia Reperfusion Injury
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Book Synopsis Mitochondrial Metabolism in Cardiac Ischemia-Reperfusion Injury by : Jimmy Zhang
Download or read book Mitochondrial Metabolism in Cardiac Ischemia-Reperfusion Injury written by Jimmy Zhang and published by . This book was released on 2018 with total page 171 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ischemia-reperfusion (IR) injury is the underlying pathology of acute myocardial infarction. The severity of IR injury is driven by mitochondrial metabolism and modulated by mitochondrial quality control mechanisms. The Krebs' cycle metabolite succinate is central to IR injury. Succinate accumulates during ischemia and its oxidation at reperfusion drives injury. The mechanism of ischemic succinate accumulation is controversial, and is proposed to involve reversal of mitochondrial complex-II. Here, using stable isotope resolved metabolomics, we demonstrated that complex-II reversal was possible in hypoxic mitochondria, but was not the primary source of succinate in hypoxic cardiomyocytes or ischemic hearts. Rather, in these intact systems succinate primarily originated from canonical Krebs' cycle activity, partly supported by aminotransferase anaplerosis and glycolysis from glycogen. Augmentation of canonical Krebs' cycle activity with dimethyl-?-ketoglutarate both increased ischemic succinate accumulation and drove substrate-level phosphorylation by succinyl-CoA synthetase, improving ischemic energetics. Although ? of ischemic succinate accumulation was extracellular, the remaining ? was metabolized during early reperfusion, wherein acute complex-II inhibition was protective. These results highlight a bifunctional role for succinate: its complex-II independent accumulation being beneficial in ischemia, and its complex-II dependent oxidation being detrimental at reperfusion. IR injury is also modulated by mitochondrial quality control mechanisms, such as autophagy. Mild mitochondrial uncoupling induces mitochondrial autophagy and both have separately been shown to protect against cardiac IR injury. However, a link between mild uncoupling and autophagy within the context of cardiac IR injury or cardioprotection has not been explored experimentally or therapeutically. Previously, we identified cloxyquin via phenotypic screening as a cardioprotective compound. Here, we demonstrated that cloxyquin mildly uncoupled mitochondria and induced autophagy. Cloxyquin-induced cardioprotection was blocked by the autophagy inhibitor chloroquine. Finally, we showed that cloxyquin-induced cardioprotection translated to an in vivo model of cardiac IR injury. Overall, these data suggest that enhanced insights into the molecular events that take place at mitochondria during ischemia may be exploited for therapeutic benefit in cardiac IR injury.
Book Synopsis Mitochondrial Metabolism in Ischemic Heart Disease by : Shijun Wang
Download or read book Mitochondrial Metabolism in Ischemic Heart Disease written by Shijun Wang and published by Frontiers Media SA. This book was released on 2022-07-27 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Ischaemia-Reperfusion Injury by : Pierce A. Grace
Download or read book Ischaemia-Reperfusion Injury written by Pierce A. Grace and published by Wiley-Blackwell. This book was released on 1999-02-04 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ischaemia-Reperfusion Injury is concerned with the consequences of interrupting and restoring blood flow to tissues. Many common clinical conditions are caused by interruption of blood flow to tissues (eg, ischaemic heart disease, peripheral vascular disease, stroke); blood flow is also interrupted deliberately in many surgical procedures (eg, cardiac surgery, arterial surgery, transplant surgery, limb surgery with tourniquet). In treating such conditions or after performing such operations the aim of the clinician is to restore the blood supply to the ischaemic tissue. Paradoxically, restoration of blood flow to ischaemic tissues can lead to further tissue damage with the potential for severe local and systemic injury. This book focuses on the clinical, pathological and biochemical processes involved in ischaemia-reperfusion injury and gives an overview of the strategies that may be adopted to mitigate or prevent such injury. This book will be of interest to both clinicians and scientists who have to deal with or have interest in this difficult but important problem.
Book Synopsis Mitochondrial Dynamics in Cardiovascular Medicine by : Gaetano Santulli
Download or read book Mitochondrial Dynamics in Cardiovascular Medicine written by Gaetano Santulli and published by Springer. This book was released on 2017-05-25 with total page 644 pages. Available in PDF, EPUB and Kindle. Book excerpt: This text covers the basic principles of mitochondrial dynamics in cardiovascular medicine, with particular emphasis on their functional roles in physiology and disease. The book will include articles pertaining to mitochondrial fitness on a global basis, providing therefore an update on the progress made in several aspects in the field. Thus, it will assist scientists and clinicians alike in furthering basic and translational research. Organized in sections focusing on: basic science, mitochondrial dysfunction in cardiac disorders, in vascular disorders, in metabolic disorders, in kidney disease, therapeutic challenges and options, this essential volume fills imperative gaps in understanding and potentially treating several cardiovascular disorders.
Book Synopsis Mitochondrial Hexokinase and Ischemic Sensitivity and Metabolism of the Heart by : Rianne Nederlof
Download or read book Mitochondrial Hexokinase and Ischemic Sensitivity and Metabolism of the Heart written by Rianne Nederlof and published by . This book was released on 2017 with total page 259 pages. Available in PDF, EPUB and Kindle. Book excerpt: "The general aim of this thesis was to study the effects of hexokinase II (HKII) on cardiac ischemia/reperfusion (I/R) injury and metabolism. In cancer cells, increased binding of both HKI and HKII have been associated with the increased survival rate of these cells. In previous studies it has been observed that binding of HKII to the mitochondria (mtHKII) protects the heart and skeletal muscle against I/R injury. This thesis focused on elucidating the cellular mechanisms by which mtHKII protects the heart against I/R injury. We focused on the effect of a reduction in mtHKII on cardiac metabolism, oxygen consumption, reactive oxygen species and the correlation between HKII and cyclophilin D (CypD). In addition, this thesis studied whether cardioprotection by remote ischemic preconditioning (RIPC) and metformin treatment in cardiac surgical patients is associated with increased amounts of mtHKII. Taken together, this thesis shows that 1) low doses (200 nM) of the special peptide TAT-HKII can be used to study effects of mtHKII reduction in the heart, 2) a reduction in mtHKII turns non-injurious I/R into injurious I/R and is accompanied by increased reactive oxygen species (ROS) production at reperfusion, and increased energetics at baseline, 3) the cardioprotective effect of CypD deletion might, at least partly, be caused by increased mtHK activity, 4) an acute, but not chronic, decrease in mtHKII affects cardiac metabolism 5) glucose-only is insufficient substrate for the Langendorff perfused mouse heart, and 6) metformin treatment and RIPC in the absence of propofol are not cardioprotective in coronary artery bypass graft (CABG) surgery under the conditions used in this thesis."--Samenvatting auteur.
Book Synopsis Reversible Protein Acetylation by : Gregory R. Bock
Download or read book Reversible Protein Acetylation written by Gregory R. Bock and published by John Wiley & Sons. This book was released on 2004-07-16 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive review of recent work on chromatin and non-histone proteins, this book arises from the interactions of a multidisciplinary group of scientists involved in the study of acetylation. This area of research opens up new and exciting possibilities for drug design, and so the final chapters in the book examine some of the potential applications in the treatment of various diseases.
Book Synopsis Reactive Oxygen Species and Mitochondrial Metabolism in Acute Myocardial Ischaemia Reperfusion Injury by : John Mulvey
Download or read book Reactive Oxygen Species and Mitochondrial Metabolism in Acute Myocardial Ischaemia Reperfusion Injury written by John Mulvey and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Mitochondria: the cell powerhouse and nexus of stress by : Sabzali Javadov
Download or read book Mitochondria: the cell powerhouse and nexus of stress written by Sabzali Javadov and published by Frontiers E-books. This book was released on 2014-09-23 with total page 122 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondrion, a sub-cellular organelle originated from primary endosymbiosis, plays a vital role in energy metabolism of eukaryotic cells. The transfer of electrons through the electron transport chain (ETC) to molecular oxygen accompanied by the extrusion of protons from the matrix generate an electrochemical gradient across the inner mitochondrial membrane (IMM) that is used for ATP synthesis by oxidative phosphorylation. Despite many aspects of ATP synthesis have been delineated, regulatory mechanisms responsible for energy synthesis and transfer still remain to be uncovered. In addition to energy function, mitochondria play a crucial role in cell metabolism under both physiological and pathological conditions through their participation in many intracellular signaling pathways. Studies over the last 30 years provide strong evidence that mitochondria are the nexus of various stresses which initiate cell death through apoptosis, oncosis, necrosis and autophagy depending on the severity of the stress and cellular energy status. The release of several pro-apoptotic proteins such as cytochrome c, Smac/DIABLO, AIF, endonuclease G from intermembrane space initiates both caspase-dependent and caspase-independent apoptosis. The formation of the mitochondrial permeability transition pore in the IMM promotes cell death mostly through necrosis whereas a mild stress activates autophagy. Due to their critical roles in both cell death and survival mitochondria have been widely considered as an important target for various pharmacological and conditional therapeutic approaches. Currently, a large number of mitochondria-targeted agents are suggested to prevent (in ischemia reperfusion injury, cardiovascular, neurodegenerative and other diseases) or stimulate (in various cancers) cell death. This Research Topic focuses on the role of mitochondria in the regulation of cell metabolism and signaling under physiological and pathological conditions. Studies performed on cultured cells and isolated organs/tissues using different animal and cellular models of various diseases are also included and discussed.
Book Synopsis Mitochondria and the Heart by : José Marín-García
Download or read book Mitochondria and the Heart written by José Marín-García and published by Springer Science & Business Media. This book was released on 2005-05-05 with total page 415 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria have been pivotal in the development of some of the most important ideas in modern biology. Since the discovery that the organelle has its own DNA and specific mutations were found in association with neuromuscular and cardiovascular diseases and with aging, an extraordi-nary number of publications have followed, and the term mitochondrial medicine was coined. Furthermore, our understanding of the multiple roles that mitochondria play in cardiac cell homeostasis opened the door for intensive experimentation to understand the pathogenesis and to find new treatments for cardiovascular diseases. Besides its role in adenosine triphosphate generation, mitochondria regu-late a complex network of cellular interactions, involving (1) generation and detoxification of reactive oxygen species, including superoxide anion, hy-drogen peroxide, and hydroxyl radical; (2) maintenance of the antioxidant glutathione in a reduced state and adequate level of mitochondrial matrix superoxide dismutase; (3) cytoplasmic calcium homeostasis, particularly under conditions of cellular calcium loading; (4) transport of metabolites between cytoplasm and matrix; (5) both programmed (apoptosis) and necrotic cell death; and (6) cell growth and development. It is therefore not surprising that this organelle has come to be the center stage in many current investigations of cardiovascular diseases, aging, and agi- related disease. Concomitant with these advances, an impressive effort is under- way for the development of new tools and methodologies to study mitochondrial structure and function, including powerful ways to visualize, monitor, and alter the organelle function to assess the genetic consequences of these perturbations.
Book Synopsis Mitochondria and Cell Death by : David M. Hockenbery
Download or read book Mitochondria and Cell Death written by David M. Hockenbery and published by Humana Press. This book was released on 2016-04-29 with total page 242 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume examines the role of mitochondria in different types of cell death, including apoptotic and necrotic cell deaths. Topics discussed include mitochondrial outer membrane permeabilization (MOMP) and the permeability transition pore; core processes such as calcium handling, fission and fusion, reactive oxygen species generation, and maintenance of mitochondrial DNA fidelity and protein folding homeostasis; and retrograde signaling between mitochondria and other cellular components, including the important role of mitochondria in antiviral immunity. The expertly authored chapters are drawn from multidisciplinary international perspectives, lending a nuanced and comprehensive approach to the material. Mitochondria and Cell Death, part of the Cell Death in Biology and Diseases series, is invaluable reading for graduate students, researchers, and clinicians in the fields of neuroscience, oncology, gastroenterology, and hepatology, as well as those interested in the study of mitochondria and cell biology.
Book Synopsis The Ischemic Heart by : Seibu Mochizuki
Download or read book The Ischemic Heart written by Seibu Mochizuki and published by Springer. This book was released on 2007-11-23 with total page 601 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past three decades, impressive progress in the field of pathogenesis, prevention and therapy of ischemic heart disease has resulted in a marked decline in mortality in the Western World. However, the incidence of this devastating disease is on the rise in developing countries. The Ischemic Heart is based upon a recent symposium in Tokyo on the subject. This volume is organized into two sections: (i) Pathophysiologic Mechanisms of Ischemia-Reperfusion Injury and (ii) Preconditioning and Protection of Ischemia-Reperfusion Injury, and contains up-to-date information concerning the current concepts of ischemia-reperfusion injury, the sequence of events resulting in the loss of contractile dysfunction, and mechanisms of cardioprotection by several drugs as well as the role of ischemic preconditioning in attenuating problems associated with ischemia-reperfusion injury.
Book Synopsis Sex Differences in Heart Disease by : Bohuslav Ostadal
Download or read book Sex Differences in Heart Disease written by Bohuslav Ostadal and published by Springer Nature. This book was released on 2020-11-15 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiovascular diseases are the leading cause of mortality in men and women. Unfortunately, women have traditionally been excluded from clinical trials, and female animals have been used less or sex was not reported in basic research studies. Until recently, consideration of both sexes was not required in clinical and preclinical studies focusing on cardiovascular diseases. However, the number of clinical and experimental papers dealing with sex differences and heart disease significantly increases during the last years. This trend is obviously the result of at least two facts: the number of examples of different behavior of the male and female heart under physiological and pathological conditions is steadily increasing and there were controversial reports on the beneficial and adverse effect of hormonal replacement therapy. Detailed molecular and cellular mechanisms of these differences are still unknown but one is clear already today: sex differences are so important that they should be considered by the selection of optimum diagnostic and therapeutic procedures in clinical practice. The book presents 16 manuscripts on sex differences of heart disease, as developed by several investigators; the volume is organized in four parts. Part I, dealing with sex differences in cardiac ischemic injury, includes 5 chapters on experimental aspects of cardiac ischemia/reperfusion injury, the role of testosterone, and clinical aspects of ischemic heart disease. Part II is devoted to sex differences in heart failure and includes four chapters. Discussion in this part of the book is centered around the sex differences in heart failure due to volume overload. Part III of this volume includes four papers on risk factors of cardiovascular diseases, namely hypertension and obesity, and, finally, three chapters in part IV deal with sex differences of cardiac mitochondria under different pathological conditions. We believe this book will be very useful for cardiovascular scientists, graduate students, postdoctoral fellows and other health professionals.
Book Synopsis Role of Mitochondrial Quality Control in Myocardial and Microvascular Physiology and Pathophysiology by : Hao Zhou
Download or read book Role of Mitochondrial Quality Control in Myocardial and Microvascular Physiology and Pathophysiology written by Hao Zhou and published by Frontiers Media SA. This book was released on 2022-11-01 with total page 199 pages. Available in PDF, EPUB and Kindle. Book excerpt: The heart is a strong muscular pump that enables tissue and organ perfusion. Therefore, a continuous supply of fresh blood is vital for cardiac function. In coronary artery disease, plaques or thrombi induce rapid occlusion, which restricts blood flow to the heart. The primary effect of coronary artery disease is substantial cardiomyocyte death, which prevents the heart from effectively pumping blood to vital organs.
Book Synopsis Mitochondrial Dysfunction by : Lawrence H. Lash
Download or read book Mitochondrial Dysfunction written by Lawrence H. Lash and published by Elsevier. This book was released on 2013-10-22 with total page 527 pages. Available in PDF, EPUB and Kindle. Book excerpt: Methods in Toxicology, Volume 2: Mitochondrial Dysfunction provides a source of methods, techniques, and experimental approaches for studying the role of abnormal mitochondrial function in cell injury. The book discusses the methods for the preparation and basic functional assessment of mitochondria from liver, kidney, muscle, and brain; the methods for assessing mitochondrial dysfunction in vivo and in intact organs; and the structural aspects of mitochondrial dysfunction are addressed. The text also describes chemical detoxification and metabolism as well as specific metabolic reactions that are especially important targets or indicators of damage. The methods for measurement of alterations in fatty acid and phospholipid metabolism and for the analysis and manipulation of oxidative injury and antioxidant systems are also considered. The book further tackles additional methods on mitochondrial energetics and transport processes; approaches for assessing impaired function of mitochondria; and genetic and developmental aspects of mitochondrial disease and toxicology. The text also looks into mitochondrial DNA synthesis, covalent binding to mitochondrial DNA, DNA repair, and mitochondrial dysfunction in the context of developing individuals and cellular differentiation. Microbiologists, toxicologists, biochemists, and molecular pharmacologists will find the book invaluable.
Book Synopsis Cardioprotection by : Derek Hausenloy
Download or read book Cardioprotection written by Derek Hausenloy and published by Oxford University Press. This book was released on 2009-08-20 with total page 138 pages. Available in PDF, EPUB and Kindle. Book excerpt: Coronary heart disease (CHD) is the leading cause of death worldwide. Cardioprotection refers to the prevention of CHD and the clinical improvement in patients suffering from cardiovascular problems.
Book Synopsis The Role of Cardiac Mitochondria in Myocardial Ischemia/reperfusion Injury by : Chad R. Frasier
Download or read book The Role of Cardiac Mitochondria in Myocardial Ischemia/reperfusion Injury written by Chad R. Frasier and published by . This book was released on 2012 with total page 182 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiovascular disease (CVD) exerts economic and humanitarian costs that are unparalleled by any other disease. Of the many etiologies of CVD, myocardial infarction accounts for over 50% of the associated mortality and anything that can decrease the extent of infarction could drastically impact the burden of CVD. The purpose of this work was to further our understanding of the role of cardiac mitochondria in ischemia/reperfusion injury. Herein I found that physiologic (exercise) and pharmacologic (Bendavia) interventions that lessen the oxidative burden during ischemia/reperfusion have the potential to limit myocardial infarction. Under conditions of oxidative stress, animals who received short term exercise (Ex) were better able to maintain the glutathione couple in a reduced state, likely through an increase in glutathione reductase (GR) activity. This phenotypic change was associated with decreased reactive oxygen species (ROS) accumulation and a lower incidence of fatal ventricular arrhythmias. Furthermore, I found that ROS generated within the cytosol, and not the mitochondria, during bouts of Ex are important signaling molecules that increase GR activity and this increased activity may be responsible for the cardioprotective effects observed with Ex. Finally, I found that treatment with the mitochondrially-targeted peptide Bendavia was successful at lowering infarct size in isolated guinea pig hearts, due to an ability to decrease ROS accumulation and maintain mitochondrial energetics. Taken together, these studies suggest that therapies aimed at decreasing mitochondrial ROS and/or maintaining mitochondrial energetics during ischemia/reperfusion may have significant clinical impact.
Book Synopsis Intra-mitochondrial Injury During Ischemia-reperfusion by : Hema Aluri
Download or read book Intra-mitochondrial Injury During Ischemia-reperfusion written by Hema Aluri and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiac injury is increased following ischemia-reperfusion. Mitochondria are the "effector organelles" that are damaged during ischemia (ISC) when there is no blood flow. Resumption of metabolism by damaged mitochondria during reperfusion (REP) results in increased cell injury. Current therapeutic interventions to pre-condition and post-condition the heart during ISC are ineffective during certain conditions like aging and diabetes due to defects in the signaling cascades. In contrast, mitochondrial-based strategies are effective in protecting the heart during ISC-REP. Hence direct therapeutic targeting of dysfunctional mitochondria will provide the potential to bypass the upstream signaling defects and intervene directly upon the effector organelle. Novel mitochondrial-targeted therapy relies on understanding the sites in the electron transport chain (ETC) that are damaged by ISC and produce cell-injury during REP. This project identifies a novel pathological role of cytochrome c in depleting cardiolipin during ischemia after which the mitochondria are in a defective condition that leads to additional cell death during reperfusion. During ischemia oxidants from complex III oxidize cytochrome c, forming a peroxidase, which causes oxidative damage and depletion of cardiolipin. Depletion of cardiolipin disrupts normal physiology and augments cell death. Identification of the innovative pathobiology during ISC-REP recognizes a novel therapeutic target, cytochrome c peroxidase, which can be a focal point for new therapeutic interventions to decrease cardiac injury. In order to maintain homeostatis, living organisms have the methionine sulfoxide reductase system, which reduce both free and protein bound Met(O) back to methionine (Met) in the presence of thioredoxin. Oxidized Trx is inactive and unable to bind to ASK1 thereby activating ASK1 and causing cell death via p38/JNK pathways thereby contributing to the pathogenesis of myocardial ISC-REP injury. In this study we have shown that inhibition of ASK1 protects the heart during REP via the modulation of mitochondria that sustained damage during ISC. The mitochondrial-based mechanism of cardioprotection with ASK1 inhibition enhanced the functional integrity of the inner mitochondrial membrane retaining cytochrome c thereby decreasing cell death. This therapeutic intervention is a key step to achieve the ultimate goal to improve clinical outcomes in patients that suffer an acute myocardial infarction.
