Wednesday, July 8, 2015

Mitochondria and the Heart






Mitochondria and the Heart
Buku ini diterbitkan tahun 2005  oleh  Springer Science+Business Media, Inc, USA
adalah buku edisi  Pertama.



Judul:  Mitochondria and the Heart
Oleh:   Jose Marin-Garcia, et al (Editor)
Penerbit:  Springer Science+Business Media, Inc, USA
Tahun: 2005
Jumlah Halaman: 411  hal.


Editor:

Jose Marin-Garcia
The Molecular Cardiology and Neuromuscular Institute,
Highland Park, New Jersey
Department of Physiology & Biophysics,
UMDNJ-Robert Wood Johnson Medical School
Piscataway, New Jersey

Michael J Goldenthal
The Molecular Cardiology Institute,
Highland Park, New Jersey

Lingkup Pembahasan:
Buku ini mengemukakan Mitokondria  paling penting dalam pengembangan dari beberapa ide penting dalam biologi modern. Sejak penemuan bahwa organel memiliki DNA sendiri dan mutasi tertentu yang ditemukan pada  hubungannya dengan neuromuskuler dan penyakit kardiovaskular dan dengan
penuaan, sebuah extraordi-nary  mengikuti jumlah publikasi, dan  istilah obat mitokondria ini diciptakan. Selain itu, pemahaman tentang peran ganda yang mitokondria bermain di jantung homeostasis sel membuka pintu untuk eksperimen intensif untuk memahami patogenesis dan untuk menemukan pengobatan baru untuk penyakit kardiovaskular.
Selain perannya dalam generasi adenosin trifosfat, mitokondria  merupakan regu-akhir jaringan kompleks interaksi seluler, yang melibatkan (1) generasi dan detoksifikasi spesies oksigen reaktif, termasuk anion superoksida, hy-Drogen peroksida, dan radikal hidroksil; (2) pemeliharaan glutathione antioksidan dalam keadaan berkurang dan tingkat yang memadai dari mitokondria matriks superoxide dismutase; (3) homeostasis kalsium sitoplasma, terutama di bawah kondisi pemuatan kalsium seluler; (4) transportasi metabolit antara sitoplasma dan matriks; (5) baik diprogram (apoptosis) dan nekrotik
kematian sel; dan (6) pertumbuhan sel dan pembangunan. Oleh karena itu tidak mengherankan bahwa organel ini telah datang untuk menjadi panggung di banyak penyelidikan saat ini penyakit kardiovaskular, penuaan, dan agingrelated penyakit. Seiring dengan kemajuan ini, upaya mengesankan cara pemahaman untuk pengembangan alat-alat baru dan metodologi untuk mempelajari struktur dan fungsi mitokondria, termasuk cara-cara ampuh untuk memvisualisasikan, memantau, dan mengubah fungsi organel untuk menilai genetik konsekuensi dari gangguan ini.

Daftar Isi:

 

1. An Introduction to Mitochondria and the Heart
    Overview 1
    What are mitochondria? 1
    How to study mitochondria: New and old 3
    Mitochondrial bioenergetics 6
    Mitochondrial biogenesis 7
    Cardiac mitochondrial changes during cardiac growth and development 9
    Mitochondria: the primary site of ROS generation and also a critical target of its
        damaging effects 10
    Mitochondrial dysfunction in cardiovascular disease 10
    Defects in mtDNA 10
    Defects in nuclear-DNA encoded mitochondrial proteins 12
    Myocardial ischemia and ETC 13
    Apoptosis and cell death 14
    Animal models of mitochondrial-associated cardiovascular disease 15
    Diagnosis and treatment of mitochondrial-based cardiac diseases 16
    The road ahead 16
    References 17
2. Mitochondrial Bioenergetics in the Heart 27
    Overview 27
    Introduction 27
    Complex I (NADH-ubiquinone oxidoreductase) 28
    Enzyme structure 29
    Complex II (Succinate-ubiquinone oxidoreductase) 30
    Complex III (Ubiquinol-cytochrome c oxidoreductase) 32
    The Q cycle and bcl function 33
    Complex IV (Cytochrome c oxidase) 35
    COX enzyme structure 36
    COX subunit gene structure and expression 37
    COX activity regulation 39
    Complex V (F0-Fi ATPase; ATP synthase) 40
    Subunit composition, structure, and function 40
    ATP synthase defects and related pathologies 44
    Other enzymes bioenergetics 45
    Adenine nucleotide translocator (ANT) 45
    ANT structure 47
    ANT regulation in the heart 47
    ANT genes and their expression 47
    ANT dysfunction plays a key role in
    cardiac pathology 48
    Creatine kinase 49
    Structure 50
    Creatine kinase and the heart 51
    PDH and the TCA (Krebs) cycle 52
    Overall regulation of mitochondrial bioenergetics in the heart 53
    Supply and demand, substrates, and oxygen and ATP-ADP levels 53
    References 56
3. Heart Mitochondrial Biogenesis 63
    Overview 63
    Introduction 63
    Structure of mtDNA 64
    MtDNA Function 66
    Replication 66
    Regulation of mtDNA replication 69
    Mitochondrial transcription and RNA processing 70
    Regulation of mitochondrial transcription and processing 72
    Mitochondrial translation 73
    Mitochondrial ribosomes 73
    Initiation and elongation of translation 76
    Mitochondria DNA repair 76
    Nuclear participation in mitochondrial biogenesis 79
    Nuclear regulatory proteins and coordination of transcriptional events 79
    Hormones affecting both mitochondrial and nuclear transcription 82
    Mitochondria import and assembly of proteins 83
    Relevance of mitochondrial biogenesis 85
    References 85
4. ROS Generation, Antioxidants, and Cell Death 99
    Overview 99
    Introduction 99
    The significance of ROS 100
    Generation of ROS 100
    Negative effect of ROS 102
    Antioxidant defense 104
    Role of ROS in cell signaling 106
    ROS and cardiac pathology 106
    ROS and apoptosis 108
    Apoptosis and cell death 109
    Myocardial apoptosis 112
    References 113
5. Myocardial Ischemia and Cardioprotection 123
    Overview 123
    Introduction 123
    Mitochondrial dysfunction in myocardial ischemia 124
    Oxidation-phosphorylation decline in ischemia 124
    Myocardial ischemia and oxidative stress 126
    Myocardial ischemia and mitochondrial calcium flux 127
    Gene expression 128
    Reperfusion 129
    Cardioprotection 129
    Ischemic cardioprotection 129
    Cascade of mitochondrial events in IPC 131
    Signaling pathways 134
    Adenosine and other ligands 134
    Activation and translocation of PKC as a pivotal signaling event in the genesis of IPC and CP 136
    Reactive oxygen species 137
    Cardioprotection: An emerging field 138
    Early and late IPC pathways 139
    Potential applications to clinical medicine 142
    References 143
6. Mitochondria Dysfunction in Cardiomyopathy and Heart failure 157
    Overview 157
    Introduction 157
    Mitochondria are the major source of bioenergy in the cardiac cell 158
    What is the evidence for myocardial dependency on mitochondrial function? 160
    Mitochondrial dysfunction and cardiomyopathy: Support from human studies 160

    Clinical evidence of nuclear mutations in mitochondrial components 165
    Constribution of transgenic models to the study of mitochondria in heart dysfunction 166
    Evidence from animals models that mitochondrial bioenergetic enzymes play a critical role in HF 168
    Mitochondrial dysfunction and other cellular pathways in cardiomyopathy 169
    Mutations in contractile/sarcomere proteins and mitochondrial function 170
    Mitochondrial function and cardiac hypertrophy 173
    Calcium signaling and mitochondrial function in HF 174
    Mitochondrial function and apoptosis in HF 174
    What events occurring in HF are truly tissue-specific? 176
    Future prospects 178
    References 179
7. Fatty Acid and Glucose Metabolism in Cardiac Disease 197
    Overview 197
    Introduction 197
    Role of fatty acids and their metabolism in the normal cardiomyocyte: Structural and regulatory
        roles in cardiac cell membranes 198
    Fatty acid transporters and glucose carriers 198
    Bioenergetics of FAO 201
    Cellular location of FAO and glucose oxidation 204
    The effect of disorders of fatty acid and glucose metabolism on cardiac structure/function 205
    Secondary effects on mitochondrial fatty acid (3-oxidation: Relationship to mitochondrial respiration
         and OXPHOS 208
    Fatty acid metabolism defects and their association with cardiomyopathy and arrhythmias 208
    Cardiomyopathy 208
    Arrhythmias and conduction defects 209
    Fatty acids, glucose, and cardiac apoptosis 210
    Abnormalities in mtDNA and their association with both diabetes and cardiomyopathy 211
    Molecular players in fatty acid-related cardiac diseases; modulation of gene expression 211
    MCAD 211
    VLCAD 212
    CPT-II 212
    MTP 212
    PPAR 213
    Peroxisome proliferator-activated receptory  coactivator (PGC- l a ) 215
    Animal models of defective fatty acid metabolism and cardiac failure 216
    Advances in diagnostics and treatment of fatty acid/cardiac disease 217
    References 218
8. Mitochondria in Pediatric Cardiology 229
    Overview 229
    MlTOCHONDRIAL CARDIOMYOPATHY 229
    Introduction 229
    Diagnosis 232
    Clinical signs 233
    Histological and electron microscopic (EM) analysis 233
    Biochemical analysis 235
    MtDNA analysis 236
    Mitochondrial tRNA mutations 236
    Mitochondrial structural gene mutations 241
    ATP synthase (ATPase6) 241
    Cytochrome b (cytb) 242
    Mutations in COX and ND subunits 243
    MtDNA depletion 244
    MITOCHONDRIA AND CONGENITAL HEART DEFECTS (CHD) 245
    Structural and functional cardiac defects 245
    Cardiac arrhythmias 246
    Other congenital cardiomyopathies with mitochondrial defects 246
    Congenital heart defects and mitochondrial respiration 247
    Conclusions 248
    References 249
9. Mitochondria and the Aging Heart 263
    Overview 263
    Introduction 264
    Bioenergetics and gene expression in the aging heart 265
    Mitochondrial function and gene expression in the aging heart 266
    ROS in the aging heart 268
    Mitochondrial DNA damage in the aging heart 270
    Rat model of cardiac aging: Defects in ETC 273
    Gene expression 275
    DNA copy number and damage analysis 275
    Comments 276
    On mitochondrial dysfunction 276
    On mitochondrial DNA damage 277
    On gene expression of mitochondrial stress proteins and cellular programming 277
    On mitochondrial PT pore 278
    Conclusions 278
    Potential approaches to reverse mitochondrial dysfunction in the aging heart 279
    References 281
10. Heart Mitochondria Signaling Pathways 289
    Overview 289
    Introduction 289
    Mitochondrial abnormalities, signaling defects, and myocardial disease 290
    Mitochondrial signaling in myocardial ischemia and cardioprotection 291
    Mitochondrial signaling and myocardial hypertrophy 294
    Signaling the mitochondria: Key players 296
    Nuclear gene activation 296
    Protein kinases 298
    Calcium signaling 300
    Mitochondrial receptors 301
    Signals of survival and stress impact heart mitochondria 302
    Survival signals and apoptosis 304
    Stress signals 306
    Metabolic signals 307
    Future prospects: Therapeutic targets and directions 307
    The essential role played by mitochondriain in cytoprotective signaling and CP 307
    Mitochondrial metabolic intermediates 308
    Summary 309
    References 310
11. Treatment of Mitochondrial-Based Cardiac Diseases: Targeting the Organelle 323
    Overview 323
    Introduction 323
    Treatment of respiratory and metabolic defects 324
    Use of antioxidants 325
    Treatment of FAO disorders, arrhythmias, and CHF 327
    Cardioprotective agents 329
    New approaches in treatment 333
    Gene therapy in cardiovascular diseases 333
    Mitochondria and gene therapy 336
    Targeting mitochondria using nucleic acids 336
    Targeting mitochondria using bioactive compounds 339
    References 340
12. Future Frontiers in Mitochondrial Cardiac Biology 351
    Overview 351
    Introduction 351
    Disease gene identification: Diagnostic application 353
    Modifying factors, Epigenetics, and SNPs 354
    Animal models of mitochondrial-based heart disease 360
    Cellular engineering 363
    Applications of stem cells in mitochondrial defects and toxicology 365
    References 367
Glossary 377
Index 388



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