Bøger i Developments in Molecular and Cellular Biochemistry serien

Cardiac cell biology has come of age. Recognition of activated or modified signaling molecules by specific antibodies, new selective inhibitors, and fluorescent fusion tags are but a few of the tools used to dissect signaling pathways and cross-talk mechanisms that may eventually allow rational drug design. Understanding the regulation of cardiac hypertrophy in all its complexity remains a fundamental goal of cardiac research. Since the advancement of adenovirally mediated gene transfer, transfection efficiency is no longer a limiting factor in the study of cardiomyocytes. A limiting factor in considering cell transplantion as a strategy to repair the damaged heart is cell availability at the right time. Cardiac gap junctions, intercellular communication channels that allow electrical and metabolic coupling and play an important role in arrhythmogenesis are now understood to be exquisite sensors of cardiac change. The reports in this volume incLude elegant studies that made use of cutting edge technological advances and many specialized reagents to address these issues.

In 1996 the 75th anniversary of the discovery of insulin was celebrated at the University of Toronto, the scene of that discovery in 1921. This volume was stimulated by the scientific program which was staged at that time and brought together much of the world's best talent to discuss and analyze the most recent developments in our understanding of pancreatic function, insulin secretion, the interaction of insulin with its target tissues, the mechanism of insulin action at the cellular level, and the defects which underlie both Type I (insulin-dependent diabetes mellitus, IDDM) and Type II (noninsulin-dependent diabetes mellitus, NIDDM) forms of the disease. We have chosen to focus the present volume on work related to insulin action.

Stress reaction is likely to play a crucial role in a variety of degenerative diseases including cancer and cardiovascular diseases. The process of stress adaptation may appear to be simple, but in reality this is a very complex process and we are only beginning to understand the mechanism of adaptation. In January, 1998, scientists from around the world assembled to discuss the potential applicability of the concept of stress adaptation in the clinical arena. This volume contains original research papers presented on this subject during the conference Stress Adaptation, Prophylaxis and Treatment held in Calcutta, India, and serves as an up-to-date source of information for scientists, as well as clinicians interested in applying the concept of stress adaptation to the cure of diseases.

The special issue of Molecular and Cellular Biochemistry focuses on `Control of Gene Expression by Catecholamines and the Renin-Angiotensin System' in health and disease. In recent years, great progress has been made in the understanding of catecholamine and angiotensin II modulated gene expression. There is also increasing evidence that catecholamine and angiotensin II induced cellular injury not solely arises from classical pathways but also from a perturbed gene expression. Taking into account that catecholamines and angiotensin II are vital for a balanced gene expression of many cells, the intriguing possibility arises that various disease are initiated or aggravated by such an imbalance. Catecholamine and angiotensin II influences can be in excess arising from, for example, hypercaloric food intake or psychosocial stress. During early progression of heart failure, sympathetic activity and angiotensin II influences also become increased. Due to beta-adrenergic receptor downregulation, depressed catecholamine influences are expected in the final stage of heart failure. An imbalanced influence of catecholamines and angiotensin II on gene expression leads to disordered molecular structures of the cell and an impaired cell function. This focused issue is organized into chapters concentrating on catecholamines, angiotensin II, and the interaction between catecholamines and angiotensin II. Basic biochemical processes are covered in detail and the potential of these pathways for explaining chronic diseases associated with excess catecholamine and angiotensin II influences should become apparent. It is hoped that this focussed issue triggers novel research into the development of drugs that are targeted at diseases characterized by an imbalanced gene expression involving catecholamines and angiotensin II.

Signal Transduction through phosphorylation and dephosphorylation of proteins in the cell is now a well-recognized mechanism involved in countless physiological and pathological processes. Consequently, the enzymes, known as protein kinases, which catalyze the phosphorylation of proteins, are critical regulators of cellular events. One of these protein kinases is the protein kinase CK2 (also known as casein kinase 2) that has been implicated in multiple functions including control of cell growth and proliferation. CK2 is a protein serine/threonine kinase which is a highly conserved and ubiquitous protein kinase. It is localized in the cytoplasmic and nuclear compartments, which accords with its multiple functional activities in the cell. Pertinent to this is also the recognition that a large number of putative substrates for this kinase have been identified in various compartments of the cell. New evidence from several laboratories has further reinforced the involvement of CK2 in signal transduction related to many cellular functions, thus underscoring the significance of its functional role in normal and abnormal cell growth and proliferation. This volume provides an overview of the state of knowledge concerning this intriguing protein kinase. It brings together contributions from leading investigators engaged in research in this field. Key developments during the past three years pertain to the elaboration of the crystal structure and definition of novel functions of the kinase, such as its role as an inhibitor of apoptosis. Additionally, the shuttling of the kinase to various compartments in response to physiological and stress stimuli appears to be a key feature of the functional regulation of its activity in the cell.

It is well established that cellular lipid binding proteins serve central roles in cellular lipid uptake and metabolism. Evidence has been presented that various metabolic diseases, such as hyperlipidemia, atherosclerosis, insulin resistance, and diabetes, are characterized by malfunctioning or deficiencies in cellular lipid binding proteins. For better understanding of the action of lipids as signaling compounds and the role of lipids in intermediary metabolism, it is essential to have detailed knowledge of the interactions between lipids and their cognant binding proteins. In view of this growing interest in lipid-protein interaction, the 4th International Conference on Lipid Binding Proteins was held in Maastricht, The Netherlands, in June 2001. The proceedings of the previous three meetings have been published in Molecular and Cellular Biochemistry. The present focused issue of Molecular and Cellular Biochemistry comprises selected papers based on the lectures and posters presented during the 4th conference, and provides insight into the significance of these proteins for the functioning of the cell.

During the last two decades, chemical and cellular studies have contributed enormously to our understanding of metal-induced carcinogenesis, and many hypotheses on the role of metals in pathophysiological processes have been investigated. In addition, new techniques are available to shed light on the mechanism of carcinogenesis in molecular terms. This conference on Molecular Mechanisms of Metal Toxicity and Carcinogenesis in September 2000 focused on the latest research in molecular mechanisms of metal-induced toxicity and carcinogenesis. The conference promoted a multidisciplinary investigative approach and included presentations from international experts on state-of-the-art information in this field.

Considering the current interest in cellular regulation and intracellular signalling systems, it is surprising that the contribution of ADP-ribosylation reactions to the modulation of a variety of specific cell processes, in parallel with other post-translational modifications such as phosphorylation, has not been generally recognized. While it is not feasible to cover all aspects of ADP-ribosylation, the thirty-one articles contained in this volume provide a valuable overview of recent progress in the field within the context of cell control mechanisms. For the convenience of the reader, the various topics have been grouped into several sections: (a) poly(ADP-ribosyl)ation; (b) mono-ADP-ribosylation; (c) toxin mono-ADP-ribosylation; (d) inhibitors and activators; (e) protein modification with ADP-ribose and its analogues; and (f) non-modification forms of ADP-ribose. The contents of the individual chapters reflect the ideas of the contributors, many of whom have spent their careers attempting to resolve the biological functions of ADP-ribosylation. We hope that this publication will serve as a useful reference for those investigators that are new to the area as well as those who are actively studying ADP-ribosylation.

Twenty years have elapsed since cytoplasmic proteins exhibiting high-affinity binding of long-chain fatty acids were first identified (Ockner et al., Science 177:56-58, 1972). These cellular fatty acid-binding proteins (FABPs) are now well established to comprise a ligand-defined group of macromolecules belonging to a family of cytoplasmic lipid binding proteins. Unique features of the FABPs are the existence of distinct types of FABP and that these are found in a variety of tissues in remarkable abundance, with some cells expressing more than one type. The physiological significance of the FABPs has only partly been elucidated. By increasing the cytoplasmic solubilization of fatty acids, the cellular FABPs are considered to function primarily in intracellular fatty acid transport, but may also be assigned important regulatory roles in cellular lipid homeostasis as well as in the modulation of cell growth and differentiation. The broad interests in cellular FABPs has led to the organization of the 1st International Workshop on Fatty Acid-Binding Protein, held in Maastricht, the Netherlands, in 1989. Prompted by the success of the first meeting, the 2nd International Workshop on Fatty-Acid-Binding Proteins, which was held again in Maastricht, on August 31 and September 1, 1992, brought together scientific scpecialists in the field of FABP research for two days of intensive and fruitful discussion. This volume is a collection of selected papers from this conference, and thus provides the state-of-the-art knowledge of cellular FABPs. The contributors to this issue represent pioneering as well as new investigators, and also reflect the multidisciplinary nature of research in this exciting and rapidly progressing field.

From somewhat enigmatic beginnings 40 years ago, guanylate cyclase research has emerged to occupy a position of prominence in the study of signal transduction. Guanylate cyclase has several intriguing features, including existence in two major forms, membrane and soluble, each independently regulated by distinct mechanisms. The membrane form gives rise to a fascinating signal transduction story important to both peptide hormones and sensory neurons. This volume covers the evolution of the field, peptide hormone receptor work, membrane guanylate cycles, related retinal diseases, and the biochemistry and physiology of the soluble form. The 16 chapters are written by leaders in the field.

CK2 is a protein serine/threonine kinase which is a highly conserved and ubiquitous protein kinase. It is localized in the cytoplasmic and nuclear compartments, which accords with its multiple functional activities in the cell. Pertinent to this is also the recognition that a large number of putative substrates for this kinase have been identified in various compartments of the cell. New evidence from several laboratories has further reinforced the involvement of CK2 in signal transduction related to many cellular functions, thus underscoring the significance of its functional role in normal and abnormal cell growth and proliferation. This volume provides an overview of the state of knowledge concerning this intriguing protein kinase. It brings together contributions from leading investigators engaged in research in this field. Key developments during the past three years pertain to the elaboration of the crystal structure and definition of novel functions of the kinase, such as its role as an inhibitor of apoptosis. Additionally, the shuttling of the kinase to various compartments in response to physiological and stress stimuli appears to be a key feature of the functional regulation of its activity in the cell.

Discusses the molecular mechanisms involved in many diseases, including Alzheimer's disease, atherosclerosis, diabetes, arthritis, and Parkinson's disease, as well as disorders of the eye, skin, cardiac, and pulmonary systems. This volume also deals with the value of dietary supplementation with antioxidants in the prevention of cellular damage.

From somewhat enigmatic beginnings 40 years ago, guanylate cyclase research has emerged to occupy a position of prominence in the study of signal transduction. This volume covers the evolution of the field, peptide hormone receptor work, membrane guanylate cycles, related retinal diseases, and the biochemistry and physiology of the soluble form.

This special issue of Molecular and Cellular Biochemistry contains original research papers as well as invited reviews dedi­ cated, on the occasion of the 40th anniversary of the inauguration of the Heart Research Group in Berlin-Buch that today forms a part there of the Max Delbriick Center for Molecular Medicine, to Professor Albert Wollenberger, founder of the Heart Research Group and for 21 years its head. The papers in this issue are written by researchers working in the field of cardiovascular research who together with Albert Wollenberger share the belief that an integrative application of advances in molecular and cellular biology will lead to new concepts for treatment and prevention of cardiovascular diseases. We hope that this special will serve as a good source of information in this regard. We wish to thank all of the contributors for their help and cooperation. We also wish to thank Mrs. Verona Kuhle for her secretarial help. We are grateful to Dr. Naranjan S. Dhalla, Editor-in-Chief of Molecular and Cellular Biochemistry for his interest and encouragement, and for agreeing to publish this issue in honor of Albert Wollenberger. ROLAND VETTER and ERNST -GEORG KRAUSE Max Delbriick Center for Molecular Medicine, Robert-Rossle-StraBe 10, 13122 Berlin-Buch, Germany PART I CARDIAC DEVELOPMENT AND REGULATION Molecular and Cellular Biochemistry 163/164: 5-11, 1996. © 1996 Kluwer Academic Publishers.

This special issue of Molecular and Cellular Biochemistry good source of information in this regard. contains original research papers as well as invited reviews We wish to thank all of the contributors for their help and dedicated, on the occasion of the 40th anniversary of the in­ cooperation. We also wish to thank Mrs. Verona Kuhle for auguration of the Heart Research Group in Beriin-Buch that her secretarial help. We are grateful to Dr. Naranjan S. Dhalla, today forms a part there ofthe Max Delbriick Center for Mo­ Editor-in-Chief of Molecular and Cellular Biochemistry for his lecular Medicine, to Professor Albert Wollenberger, founder interest and encouragement, and for agreeing to publish this of the Heart Research Group and for 21 years its head. issue in honor of Albert Wollenberger. The papers in this issue are written by researchers work­ ing in the field of cardiovascular research who together with ERNST-GEORG KRAUSE and ROLAND VETTER Albert Wollenberger share the belief that an integrative ap­ Max Delbriick Center for Molecular Medicine plication of advances in molecular and cellular biology will Robert-Rossle-StraBe 10 lead to new concepts for treatment and prevention of cardio­ 13122 Beriin-Buch vascular diseases. We hope that this special will serve as a Gennany ALBERT WOLLENBERGER, Professor, Ph. D. (Harvard), Dr. Sc. Med. (Berlin) The dedication is accorded to Prof.

The multiplicity of receptor types, G-proteins, effector proteins, second messengers and protein kinases, their substrate proteins and the `cross-talk' interactions in the myocardium raises fundamental questions about the mechanisms that ensure the precision and timing of the myocardial responses to hormonal and pharmacological stimuli.

the GABA increase takes place and (2) the area of the brain that may mediate the anticonvulsant Investigation of the physiology, biochemistry, activity. Three compounds that increase brain pharmacology and anatomy of GAB A and GABA­ GABA by distinct mechanisms were used in these containing neural systems, continues to reveal the studies: di-n-propylacetate (DPA, sodium val­ rich complexities associated with this neuroactive proate, Depakene(R)), amino-oxyacetic acid amino acid (see recent symposia 1,2,3). Advances (AOAA) and y-vinyl GABA (GVG). in the pharmacology of GABA-mimetic agents In the next sections, the metabolism of GABA have resulted in the development of compounds and a brief historical account of the relationship that can selectively activate GABA receptors (4,5, between GABA and anticonvulsant activity are 6, 7), inhibit the synthetic and degradative enzymes outlined followed by a discussion ofthe biochemical for GABA (8, 9) or affect the neuronal and glial and pharmacological effects of the three drugs. In uptake processes for GABA (10, 11). This has particular, the literature pertaining to the suppres­ already had a significant impact on our under­ sion of seizures and the correlation between anti­ standing of the role of GABA in convulsions and a convulsant action and increases in brain G ABA will range of other CNS functions including feeding be examined. (12), cardiovascular control (13), motor activity (14) and release of pituitary hormones (15). Before 1.

This volume explores all aspects of vascular biochemistry and includes chapters that provide an understanding of vascular function with descriptions of tissue components present in the vascular wall as well as an exploration of the hemodynamic and metabolic activities associated with this function.

The articles summarize the current scientific knowledge of these compounds with reference to relevant clinical conditions, and discuss the chemical, biological, and clinical functions of these compounds.