ISSN:0892-6638    

DOI:10.1096/fasebj.4.9.2347463

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Even though oxygen is necessary for aerobic life, it can also participate in potentially toxic reactions involving oxygen free radicals and transition metals such as Fe that damage membranes, proteins, and nucleic acids. Oxygen free radical reactions and oxidative damage are in most cases held in check by antioxidant defense mechanisms, but where an excessive amount of oxygen free radicals are produced or defense mechanisms are impaired, oxidative damage may occur and this appears to be important in contributing to several pathological conditions including aging, carcinogenesis, and stroke. Several newer methods, such as in vivo spin‐trapping, have become available to monitor oxygen free radical flux and quantitate oxidative damage. Using a combination of these newer methods collectively focused on one model, recent results show that oxidative damage plays a key role in brain injury that occurs in stroke. Subtle changes, such as oxidative damage‐induced loss of glutamine synthetase activity, may be a key event in stroke‐induced brain injury. Oxygen free radicals may play a key role in carcinogenesis by mediating formation of base adducts, such as 8‐hydroxyguanine, which can now be quantitated to very low levels. Evidence is presented that a new class of free radical blocking agents, nitrone spin‐traps, may help not only to clarify if free radical events are involved, but may help prevent the development of injury in certain pathological conditions.—Floyd, R. A. Role of oxygen free radicals in carcinogenesis and brain ischemia.FASEB J.4: 2587‐2597, 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.9.2189775

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Tenascin and fibronectin are two major extracellular matrix glycoproteins. They both consist of large disulfide‐linked subunits composed of multiple structural domains. More than half of each molecule consists of so‐called fibronectin type III repeats, but the other domains differ. Fibronectin is a dimer, whereas tenascin is a hexamer. Often fibronectin and tenascin are colocalized in tissues, but the occurrence of tenascin is much more restricted when compared with fibronectin. Tenascin is transiently expressed in many developing organs such as connective tissues, the mesenchyme of epithelial organs, and also the central and peripheral nervous systems, and it reappears in the stroma of many tumors. The distinctive and highly regulated expression of tenascin has provoked interest in trying to identify possible functions of tenascin in cell‐cell and cell‐substratum adhesion, cell migration, growth, and cell differentiation during morphogenesis.—Chiquet‐Ehrismann, R. What distinguishes tenascin from fibronectin?FASEB J.4: 2598‐2604; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.9.1693347

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

For many years, investigators have been concerned with mechanisms that control and alter genetically regulated development. An intriguing aspect of these mechanisms is the ability of environmental factors to induce certain metabolic processes. Animal studies have shown that dietary manipulation of cholesterol and fatty acid metabolism during development can have persistent and permanent effects. In addition, there appears to be a critical period when changes in the diet can have lasting consequences. The changes in the control exerted by nutritional factors on metabolic development coincide with three phases of development: prenatal, suckling, and weaning. The effects of diet on cholesterol and fatty acid metabolism throughout these three phases of development will be addressed in this review.— Little, M.‐T. E.; Hahn, P. Diet and metabolic development.FASEB J.4: 2605‐2611, 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.9.2189776

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Guanine nucleotide binding proteins (G proteins) play key roles in signal transduction, including the coupling of hormone and neurotransmitter receptors to adenylate cyclase, ion channels, and polyphosphoinositide metabolism. One member of this family of proteins, Gs, appears to represent a specific site of action of ethanol in the central nervous system. Ethanol is often perceived as a nonspecific drug, and its anesthetic effects may in fact arise from relatively nonspecific interactions with cell membrane lipids. However, recent investigations point to a selective effect of low concentrations of ethanol to promote the activation of Gs, and thus to enhance adenylate cyclase activity. Ethanol seems to have little or no effect on the function of other identified G proteins. After chronic ingestion of ethanol by animals, or chronic exposure of cells in culture to ethanol, the sensitivity of adenylate cyclase to stimulation by guanine nucleotides and agonists that act via Gsis decreased. The mechanism of this change may involve qualitative and/or quantitative alterations in Gs, and seems to vary in different cell types. Studies of human platelets and lymphocytes also reveal differences in adenylate cyclase activity between alcoholics and control subjects.∗∗∗ The differences are consistent with involvement of Gs, and do not appear to reverse upon cessation of alcohol exposure. The results suggest that the platelet and/or lymphocyte adenylate cyclase system may provide a biochemical marker of genetic predisposition to alcoholism.—Hoffman, P. L.; Tabakoff, B. Ethanol and guanine nucleotide binding proteins: a selective interaction.FASEB J.4: 2612‐2622, 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.9.2161371

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

A central goal in membrane biology is to understand how channel proteins work in terms of their underlying protein structures. Ionic channels are symmetric (or pseudosymmetric) transmembrane protein assemblies organized around a central aqueous pore. The two key functional elements are the ionic channel, the actual polar pathway that permits the selective passage of 108ions per second across the apolar core of the membrane lipid bilayer, and the sensor, the structure that detects the stimulus and couples it to the opening or closing (gating) of the channel. The current excitement in membrane protein science emerges from structural information that is providing clues about the molecular determinants of function: molecular cloning and sequencing has led to the elucidation of the primary structures of several superfamilies of voltage‐gated and ligand‐gated channels; channel proteins have been purified and reconstituted in lipid bilayers with full retention of function; the properties of many channel proteins have been characterized at the single‐channel level; cDNA or RNA transcripts have been expressed in oocytes as functional proteins; specific peptide sequences predicted by molecular modeling to form the channel lining have been synthesized by solid‐phase methods and proved to be channel formers in lipid bilayers. These advances are beginning to delineate general principles about the molecular design of this class of proteins that are essential for cellular excitability and signal transduction.— Montal, M. Molecular anatomy and molecular design of channel proteins.FASEB J.4: 2623‐2635; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.9.1693348

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

The amino acid receptor proteins are ubiquitous transducers of most excitatory and inhibitory synaptic transmission in the brain. In July 1987 two reports appeared describing the molecular cloning of a pair of subunits of the GABAAreceptor (7) and one subunit of the glycine receptor (13). These papers sparked wide interest and led quickly to the concept of a ligand‐gated receptor‐ion channel superfamily that includes nicotinic acetylcholine receptors as well as certain amino acid receptors. The identification of additional subunits of each receptor followed; with the recent cloning of a kainate receptor subunit (14), only the NMDA receptor remains elusive. Several disciplines have been brought to bear on these receptor clones, including in situ hybridization and functional expression inXenopus laevisoocytes and mammalian cell lines. In this review we compare cloning strategies that have been used for amino acid receptors and discuss structural similarities among the receptor subunits. Two findings that have arisen from molecular cloning and expression of these receptors receive special attention. First, the molecular heterogeneity of GABAAreceptors is larger than expected from pharmacological studies of native receptors. Second, although the native receptors are thought to be heterooligomers, much like the model proposed for the nicotinic receptors, some individual amino acid receptor subunits can form functional receptor channels, presumably in a homomeric configuration. This review focuses, therefore, on what we have learned from cloning efforts about amino acid receptors and what might lie ahead in this field.—Dingledine, R.; Myers, S. J.; Nicholas, R. A. Molecular biology of mammalian amino acid receptors.FASEB J.4: 2636‐2645, 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.9.2161372

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Systemic lupus erythematosus (SLE) is considered a classical autoimmune disease that involves many biological systems. Similar to other autoimmune conditions, its etiology is multifactorial entailing genetic, environmental, hormonal, and immunologic factors. In this review we demonstrate that by using a pathogenic idiotype of anti‐DNA autoantibodies, it is possible to explain some of the pathogenesis and diversity of clinical and serological manifestations reported by SLE patients. The 16/6 idiotype (Id) is a representative pathogenic idiotype of anti‐DNA autoantibodies. The serum titers of 16/6 Id in SLE patients correlate with clinical activity of the disease, and are deposited in afflicted tissues in SLE patients. SLE was experimentally induced in naive mice after immunization with 1 μg of the Id. The disease is characterized clinically (proteinuria), serologically (e.g., anti‐dsDNA, anti‐Sm antibodies), and by pathological findings (e.g., deposition of 16/6 Id in the kidneys). The condition can be induced by other human and mouse antibodies carrying the 16/6 Id, as well as by mouse antimonoclonal‐16/6 Id and by T cell lines and clones specifically reactive with 16/6 Id. There are strain‐dependent differences in susceptibility to the induction of systemic lupus erythematosus (SLE). Induction of SLE is directly correlated with the ability to respond to the 16/6 idiotype (or 16/6 Id)2by anti‐Id antibody production. It is easier to induce the disease in females, and it can be modulated by manipulation of sex hormones. Being able to identify the pathogenic idiotype allowed us to generate T suppressor (Ts) cells specific for the 16/6 Id. Treatment of mice with these T cells abrogated the disease. Our studies point to the importance of pathogenic idiotypes of autoantibodies in autoimmunity, which suggests that SLE may represent a dysregulation of a functional network of idiotypes‐anti‐idiotypes interactions among autoreactive B cells, T helper cells, and T suppressor cells.— Shoenfeld, Y.; Mozes, E. Pathogenic idiotypes of autoantibodies in autoimmunity: lessons from new experimental models of SLE.FASEB J.4: 2646‐2651; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.9.2140806

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Fructose, a naturally occurring hexose, is a component of many fruits, vegetables, and sweeteners. Because of the introduction of high fructose corn sweeteners in 1967, the amount of free fructose in the diet of Americans has increased substantially in the last 20 years. Fructose is sweeter, more soluble, and less glucogenic than glucose or sucrose, so it has been recommended as a replacement for these sugars in the diets of diabetic and obese people. Although an acute dose of fructose causes smaller increases in glucose and insulin than a comparable dose of glucose, there are a number of changes after dietary adaptation that may reduce its desirability as a sugar replacement in certain segments of the population. Fructose is absorbed primarily in the jejunum and metabolized in the liver. When consumed in excess of dietary glucose, it may be malabsorbed. Fructose is more lipogenic than glucose or starches, and usually causes greater elevations in triglycerides and sometimes in cholesterol than other carbohydrates. Dietary fructose has resulted in increases in blood pressure, uric acid, and lactic acid. People who are hypertensive, hyperinsulinemic, hypertriglyceridemic, noninsulin‐dependent diabetic, or postmenopausal are more susceptible to these adverse effects of dietary fructose than healthy young subjects. Although consumption of fructose as a component of fruits and vegetables is an unavoidable consequence of eating a healthy diet, added fructose seems to provide little advantage over other caloric sweeteners and compares unfavorably to complex carbohydrates in susceptible segments of the population.— Hallfrisch, J. Metabolic effects of dietary fructose.FASEB J.4: 2652‐2660; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.9.2189777

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

In previous work we showed that programed cell death (PCD) in thymocytes is mediated by a sustained increase in cytosolic Ca2+concentration, resulting in the activation of an endogenous endonuclease, DNA fragmentation, and cell death. In this study we investigated the roles of Ca2+and DNA fragmentation in target cell killing by natural killer (NK) cells. The effector cells induced a rapid, sustained increase in cytosolic Ca2+concentration in Jurkat target cells. Buffering the target cell cytosolic Ca2+with the Ca2+‐selective dye, quin‐2, prevented target cell killing. Extensive DNA fragmentation was associated with killing in every target tested, and this response was also blocked by quin‐2. The endonuclease inhibitor, aurintricarboxylic acid, inhibited both DNA fragmentation and killing without influencing the Ca2+increase in target cells. Thus, it is concluded that NK cell killing depends on a Ca2+increase and appears to involve endogenous endonuclease activation in target cells.— McConkev. D. J.; Chow, S. C.; Orrenius, S.; Jondal, M. NK cell‐induced cytotoxicity is dependent on a Ca2+increase in the target.FASEB J.4: 2661‐2664; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.9.2347464

出版商:Wiley    

年代:1990

数据来源: WILEY