ISSN:0892-6638    

DOI:10.1096/fasebj.5.7.2010054

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Cells are exposed during their lifetimes to an array of physical forces ranging from those generated by association with other cells and extracellular matrices to the constant forces placed on cells by gravity. Alterations in these forces, either with differentiation and development or changes in activity or behavior, result in modifications in the biochemistry and adaptation in structure and function of cells. Also, a variety of differentiated cells have unique shapes that relate to extremely specialized functions, with structure and function emerging concurrently. These observations lead to the concept that the forces perceived by cells may dictate their shape, and the combined effects of external physical stimuli and internal forces responsible for maintaining cell shape may stimulate alterations in cellular biochemistry. This review examines the state of our knowledge concerning the mechanisms through which physical forces are converted to biochemical signals (mechanotransduction), and speculates on the molecular structures that may be involved in mechanotransduction.—Watson, P. A. Function follows form: generation of intracellular signals by cell deformation.FASEB J.5: 2013–2019; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.7.1707019

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

To investigate the influence of alterations in protein synthetic and degradative rates to the regulation of muscle mass, a variety of laboratory techniques have been developed in order to estimate the rates of total protein and individual contractile protein turnover in the intact experimental animal. These techniques are based on well‐established methods of compartmental analysis, and rely on the intravenous administration and biosynthetic incorporation of radiolabeled amino acids into newly synthesized muscle proteins. In this review, the two most widely used procedures (the constant and flooding infusion methods) are examined with respect to the major assumptions and pitfalls in the two procedures. The theoretical and practical limitations of these biosynthetic labeling techniques are critically analyzed with the aim of providing a clear rationale for the application of these techniques to the future study of skeletal and cardiac muscle growth and atrophy in vivo.—Samarel, A. M. In vivo measurements of protein turnover during muscle growth and atrophy.FASEB J.5: 2020–2028; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.7.2010055

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Endothelial dysfunction occurs after myocardial ischemia and reperfusion characterized by a marked reduction in endothelium‐dependent relaxation (EDR) due to reduced release or action of endothelium‐derived relaxing factor (EDRF). This reduced EDR occurs in coronary rings isolated from cats 2.5 min after reperfusion and in isolated perfused cat hearts 2.5 min after reperfusion. No decrease in EDR occurs before reperfusion in either preparation, suggesting that this impairment in EDR occurs during reperfusion. The decrease in EDR occurs soon after the generation of superoxide radicals by the reperfused coronary endothelium. Accumulation of neutrophils and myocardial cell injury does not occur until 3–4.5 h after reperfusion. Thus, endothelial generation of superoxide radicals acts as a trigger mechanism for endothelial dysfunction which is then amplified by neutrophil adherence and diapedesis into the ischemic region enhancing post‐reperfusion ischemic injury. Agents that preserve endothelial function or inhibit neutrophil activation (e.g., superoxide dismutase, prostacyclin analogs, TGF‐β, antibodies to adhesive proteins) can protect against endothelial dysfunction and myocardial injury, if administered before reperfusion.—Lefer, A. M.; Tsao, P. S.; Lefer, D. J.; Ma, X.‐1. Role of endothelial dysfunction in the pathogenesis of reperfusion injury after myocardial ischemia.FASEB J.5: 2029–2034; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.7.2010056

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

The nature of drug agonism has been the central mystery of two conceptually different approaches: classical receptor theory, which does not requite any knowledge of mechanism, and mechanistic theories, which do. Ligand‐activated ion channel macromolecules that contain both the agonist receptor site and molecular machinery to generate a response present a unique experimental system with which to explore agonism and antagonism. Electrical recordings from one channel at a time offer phenomena and a perspective quite different from that usually encountered in studies of the drug‐receptor interaction. This review describes patch‐clamp recordings thai illustrate the ligand‐evoked behavior that gives rise to classical phenomena. A comparison of the channel currents recorded in the presence of different agonists reveals how these drugs act as full or partial agonists. At higher concentrations of agonist, the conformational and kinetic transitions that underlie desensitization can be observed. Receptor conformational changes induced by agonist and antagonist binding further expand our ideas about what these drugs do, and contribute to the growth of concepts that will further our understanding of drug agonism.—Pallotta, B. S. Single ion channel's view of classical receptor theory.FASEB J.5: 2035–2043; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.7.1707020

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Gene regulation by steroid hormones is accomplished by a variety of different mechanisms leading to induction or repression of particular genes. These mechanisms are all mediated by a single class of intracellular hormone receptors, which in the unliganded state are maintained in an inactive form by association with other cellular proteins, including hsp90. Induction of the mouse mammary tumor virus (MMTV) requires binding of the hormone receptor to a hormone‐responsive element (HRE) that is precisely organized in a phased nucleosome. After receptor binding, changes in chromatin structure are detected that correlate with binding of transcription factors, including nuclear factor I, to the MMTV promoter. However, although nuclear factor I acts as a basal transcription factor on the MMTV promoter it does not cooperate with the hormone receptors in terms of binding to free DNA, and mutation of the nuclear factor I binding site does not eliminate hormonal stimulation. This residual induction is mediated by octamer motifs upstream of the TATA box that bind the ubiquitous transcription factor OTF‐1. Mutation of these octamer motifs does not influence basal transcription in vitro, but completely abolishes the stimulatory effect of progesterone receptor. Glucocorticoids also inhibit expression of many genes. The effect on the gene for the α‐subunit of chorionic gonadotropin is due to DNA binding competition between the receptor and the protein mediating cAMP induction, whereas repression of the collagenase gene involves an interaction of the receptor with components of the API complex, Jun and Fos.—Beato, M. Transcriptional control by nuclear receptors.FASEB J.5: 2044–2051; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.7.2010057

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

More than 70 mutations in the two structural genes for type I procollagen (COL1A1 and COL1A2) have been found in probands with osteogenesis imperfecta, a heritable disease of children characterized by fragility of bone and other tissues rich in type I collagen. The mutations include deletions, insertions, RNA splicing mutations, and single‐base substitutions that convert a codon for glycine to a codon for an amino acid with a bulkier side chain. With a few exceptions, the most severe phenotypes of the disease are explained largely by synthesis of structurally defective proa chains of type I procollagen that either interfere with the folding of the triple helix or with self‐assembly of collagen into fibrils. The results emphasize the extent to which the zipperlike folding of the collagen triple helix and the self‐assembly of collagen fibrils depend on the principle of nucleated growth whereby a few subunits form a nucleus and the nucleus is then propagated to generate a large structure with a precisely defined architecture. The principle of nucleated growth is a highly efficient mechanism for the assembly of large structures, but biological systems that depend extensively on nucleated growth are highly vulnerable to mutations that cause synthesis of structurally abnormal but partially functional subunits. Recently, several mutations in three other collagen genes (COL2A1, COL3A1, and COL4A5) have been found in probands with genetic diseases involving tissues rich in these collagens. Most of the probands have rare genetic diseases but a few appear to have phenotypes that are difficult to distinguish from more common disorders such as osteoarthritis, osteoporosis, and aortic aneurysms. Therefore, the results suggest that mutations in procollagen genes may cause a wide spectrum of both rare and common human diseases.—Kuivaniemi, H.; Tromp, G.; Prockop, D. J. Mutations in collagen genes: causes of rare and some common diseases in humans.FASEB J.5: 2052–2060; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.7.2010058

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Many approaches have been used to study short‐ and long‐term memory. Bacteria detect chemical gradients using a memory obtained by the combination of a fast excitation process and a slow adaptation process. This model system, which has the advantages of extensive genetic and biochemical information, shows no features of long‐term memory. To study long‐term memory, neural cell line systems have been developed that exhibit two phenomena associated with learning and memory, habituation and potentiation. The expression of these phenomena in clonal cell lines, devoid of synaptic connections, makes it possible to study the biochemical and molecular mechanisms that contribute to short‐term and long‐term memory.—Morimoto, B. H.; Koshland, D. E., Jr. Short‐term and long‐term memory in single cells.FASEB J.5: 2061–2067; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.7.2010059

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Many lipids or lipid‐derived products generated by phospholipases acting on phospholipids in membranes are implicated as mediators and second messengers in signal transduction. Our current understanding of the primary sequence relationships within the class of extracellular phospholipase A2's and among the numerous forms of the mammalian phosphatidylinositol‐specific phospholipase C's is reviewed. New results suggesting roles for these phospholipases as well as other phospholipases such as phospholipase C and D acting on phosphatidlycholine in generating arachidonic acid for eicosanoid biosynthesis, inositol phosphates for Ca2+mobilization, and diglyceride for protein kinase C activation through receptor‐mediated processes, are discussed. In addition, the possible role of phospholipases acting on sphingolipids such as sphinglomyelinase in generating lipid mediators is considered.—Dennis, E. A.; Rhee, S. G.; Billah, M. M.; Hannun, Y. A. Role of phospholipases in generating lipid second messengers in signal transduction.FASEB J.5: 2068–2077; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.7.1901288

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Low‐light digitized video fluorescence polarization microscopy was used to measure lipid order parameters in plasma membrane blebs of single, cultured rat hepatocytes during ATP depletion with the metabolic inhibitors cyanide and iodoacetic acid. Hepatocytes were labeled on the microscope stage with the plasma membrane probe trimethylammoniumdiphenylhexatriene at successive stages of cell injury. A pair of fluorescence polarization ratio images was obtained from a series of four fluorescence images recorded with a polarizer in the emission path oriented first parallel and then perpendicular to each of two orthogonal excitation light polarization directions. From the polarization ratio images, the lipid order parameter S was determined in individual plasma membrane blebs. Results indicate that the plasma membrane becomes uniformly rigid within a few minutes of the addition of metabolic inhibitors when small surface blebs have formed and ATP levels have fallen by>95%. The measured order parameter of S ã 0.95 in plasma membrane blebs, compared with S ã 0.75 in normoxic cell plasma membranes, remained unchanged throughout the course of bleb development and ultimate cell death. These findings demonstrate that significant alteration in hepatocyte plasma membrane structure occurs early in hypoxic cell injury.—Florine‐Casteel, K.; Lemasters, J. J.; Herman, B. Lipid order in hepatocyte plasma membrane blebs during ATP depletion measured by digitized video fluorescence polarization microscopy.FASEB J.5: 2078–2084; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.7.2010060

出版商:Wiley    

年代:1991

数据来源: WILEY