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In the past few years there has been the increased recognition that the effects of oxidative stress are not limited to the damage of cellular constituents. There is now evidence that reactive oxygen species (ROS) can alter cell function by acting upon the intermediates, or second messengers, in signal transductions. Such effects on signaling mechanisms probably account for the role of oxidative stress in inflammation, aging, and cancer. This volume brings together internationally recognized researchers in both the major areas covered by the book, oxidative stress and signal transduction. The work is organized in three sections. The first deals with the immediate cellular responses to oxidative stress and the production of second messengers. The second details the connection between second messengers and the gene. The third part looks more closely at the level of the gene.

Platelets playa fundamental, life-saving role in hemostasis and blood clotting at sites of vascular injury. Unwanted platelet activation and arterial thombus formation are, however, implicated in the onset of myocardial infarction, stroke, and other cardiovascular diseases. Acceptance that platelets play a major role in the pathogenesis of atherosclerosis including coronary heart disease has revolutionized the pharmacological treatment of cardiovascular diseases, and aspirin is now an essential antiplatelet drug and the golden standard for future developments. Yet the search for better and perhaps safer antiplatelet drugs is one of the most active areas of investigation in both basic and clinical research. Platelets, especially human platelets, have also emerged as one of the major models for the study of inter- and intracellular signal transduction pathways. Many biochemists, cell biologists, pharmacologists, pathologists, hematologists, and cardiologists find platelets useful for studying processes such as adhesion, inside-out and outside-in signalling through the plasma membrane, channels, calcium homeostasis, protein kinases, the network of intracellular signal transduction cascades, and the release of vasoactive substances. The aim of the editors has been to compile chapters summarizing the current state-of-the-art information on the biochemistry, cell biology, pharmacology, and physiologic and pathophysiologic roles of human platelets. We hope that this volume represents the major aspects of current platelet research although it is perhaps inevitable that certain areas are covered less thoroughly than others. We would like to acknowledge the excellent help and support of the Springer-Verlag staff, in particular that of Ms. Doris Walker.

This must-have cell signaling title will appeal to researchers across molecular biology, biochemistry, cell biology and genetics. The articles are written and edited by experts in the field and emphasize signaling to and from intracellular compartments including transcriptional responses to cytoplasmic and nuclear signaling events, chromatin remodeling and stress responses, the regulation of endoplasmic reticulum function, control of cell cycle progression and apoptosis and the modulation of the activities of mitochondria and other organelles. - Articles written and edited by experts in the field - Thematic volume covering regulation of endoplasmic reticulum function, regulation of cell cycle progression, and quality control and assurance in mitochondrion events - Up-to-date research on events in membrane proteins and proteins of intracellular matrix

Provides a comprehensive overview of recent discoveries and current understandings of G protein-coupled receptors (GPCRs). Recent advances include the first mammalian non-rhodopsin GPCR structures and reconstitution of purified GPCRs into membrane discs for defined studies, novel signaling features including oligomerization, and advances in understanding the complex ligand pharmacology and physiology of GPCRs, in new assay technologies and drug targeting. The authors take time to detail the importance of the pathophysiological function and drug targeting of GPCRs, specifically β-adrenoceptors in cardiovascular and respiratory diseases, metabotropic glutamate receptors in CNS disorders, S1P receptors in the immune system, and Wnt/Frizzled receptors in osteoporosis. This book will be invaluable to researchers and graduate students in academia and industry who are interested in the GPCR field.

This volume, along with its companion (volume 474), presents methods and protocols dealing with thiol oxidation-reduction reactions and their implications as they relate to cell signaling. The critically acclaimed laboratory standard for 40 years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Over 450 volumes have been published to date, and much of the material is relevant even today--truly an essential publication for researchers in all fields of life sciences. - Along with companion volume, provides a full overview of techniques necessary to the study of thiol redox in relation to cell signaling - Gathers tried and tested techniques from global labs, offering both new and tried-and-true methods - Relevant background and reference information given for procedures can be used as a guide to developing protocols in a number of disciplines

Apoptosis, Cell Signaling, and Human Diseases: Molecular Mechanisms, Volumes 1 & 2, present a concise synthesis of recent developments in the understanding of both cell survival and apoptotic pathways. Particular attention is given to apoptosis in human diseases, such as different forms of cancer and neurodegenerative diseases. These comprehensive volumes integrate the most innovative and current findings from several related disciplines of scientific research, including pathology, genetics, virology, cell biology, immunology, and molecular biology. Volume 1 is divided into two sections:'Malignant Transformation and Metastasis'and'Molecular Basis of Disease Therapy.'Volume 2 follows a similar structure and is divided into sections entitled'Kinases and Phosphate'and'Molecular Basis of Cell Death.'All of the contributors are at the forefront of scientific discovery, and the reviews they present systemically examine the most exciting and innovative aspects of their particular areas of expertise. Researchers will find these volumes of major benefit as they search for novel and more effective treatments for human diseases.

Complex and unexplained phenomena tend to foster unorthodox perspectives. This publication is an example, as is a prior publication that emphasized the concept that intermediary metabolism might play a significant and determining role in hepatocyte proliferation and 1 tumorigenesis. Formulation of this hypothesis was based on an attempt to clarify several poorly understood phenomena; including the observations: 1) that xenobiotic peroxisome proliferators such as the fibrate hypolipidemic agents induce hepatocyte proliferation and carcinogenesis in rodents; 2) that benign and malignant liver tumors complicate the human syndrome of glycogen storage disease type I (glucose-6-phosphatase deficiency); and 3) that in this same syndrome, administration of glucose exerts an anti-tumor effect. Fatty acid and glucose metabolism are tightly linked in a we- established and profoundly inportant interplay. This connection, together with the fact that peroxisome proliferator-induced hepatocyte proliferation and carcinogenesis reflects inhibition of mitochondrial carnitine palmitoyltransferase-I and fatty acid oxidation, suggested the possibility that regulation of fatty acid metabolism could prove to be a pivotal determinant in the control of cell growth. In 1993, the year in which the paper cited above was published, insight into the importance of growth factors and signal transduction pathways in cell cycle regulation was increasing rapidly, but metabolic and energetic aspects of cell proliferation had attracted relatively little attention. Despite this, the concept seemed inescapable that the two seemingly distinct and unrelated determinants — signal transduction and metabolism — were integrally linked.

In is now understood that the response of mammalian cells to a wide variety of potentially toxic agents may be intimately linked with many human diseases, including rheumatoid arthritis, ischemia, fever, infection, and cancer. In Stress Response: Methods and Protocols, Stephen Keyse has assembled a diverse collection of readily reproducible methods devoted to the study of these varied and powerful responses. Written by leading researchers expert in the techniques they describe, these detailed methods cover the detection and assay of stress-induced damage, the activation of a wide range of signal transduction pathways by cellular stress, stress-induced gene expression, and stress protein function. To ensure experimental success, step-by-step guidance is provided for each method, along with details of reagents, equipment, and other requirements. The methods include both well-established techniques and new technologies at the leading edge of research. Wide ranging and highly practical, Stress Response: Methods and Protocols provides a gold-standard bench manual for today's basic and clinical scientists working to understand how cells and tissues respond during physiological stress and in human disease.