ISSN:0892-6638    

DOI:10.1096/fasebj.3.8.2721854

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Activation of a variety of cell surface receptors results in the phospholipase C‐catalyzed hydrolysis of the minor plasma membrane phospholipid phosphatidylinositol 4,5‐bisphosphate, with concomitant formation of inositol 1,4,5‐trisphosphate and diacylglycerol. There is strong evidence that inositol 1,4,5‐trisphosphate stimulates Ca2+release from intracellular stores. The Ca2+‐releasing actions of inositol 1,4,5‐trisphosphate are terminated by its metabolism through two distinct pathways. Inositol 1,4,5‐trisphosphate is dephosphorylated by a 5‐phosphatase to inositol 1,4‐bisphosphate; alternatively, inositol 1,4,5‐trisphosphate can also be phosphorylated to inositol 1,3,4,5‐tetrakisphosphate by a 3‐kinase. Although the mechanism of Ca2+mobilization is understood, the precise mechanisms involved in Ca2+entry are not known; the proposal that inositol 1,4,5‐trisphosphate secondarily elicits Ca2+entry by emptying an intracellular Ca2+pool is considered.—Putney, J. W., Jr.; Takemura, H.; Hughes, A. R.; Horstman, D. A.; Thastrup, O. Howdo inositol phosphates regulate calcium signaling?FASEB J.3: 1899‐1905; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.8.2542110

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

The second half of the 1980s is certain to be considered a turning point in the study of ion channels. Within the last few years, monumental advances in the application of molecular biology, single‐channel recording, and direct molecular characterization have been brought to bear on the problem of relating the molecular structure of the ion channel proteins to their function in the cell membrane. Structure‐function relationships can now be studied at a level of detail that was unimagined a decade ago. Recently, advances made with the techniques of molecular biology appear to have dominated the literature in this field; however, innovative strategies of structural characterization and electrical measurements of functioning channels in native and artificial membranes continue to break new ground. This paper is a selective review of current progress in understanding structure‐function relationships in ion channels. The relative usefulness of determining amino acid sequences of channel proteins together with the resulting deductions about 3‐dimensional structure and function will be evaluated with respect to the potential importance of studying the channel molecules more directly by biochemical, immunological, and electrophysiological methods. A full understanding of the details of channel structure and its relationship to function may be realized in the near future as a result of the interdisciplinary application of biophysical, biochemical, and molecular biological techniques.— Krueger, B. K. Toward an understanding of structure and function of ion channels.FASEB J.3: 1906‐1914; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.8.2470631

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

The structure of the polypeptide chains and oligosaccharide moieties of the a and β subunits of pituitary and placental glycoprotein hormones are known. The dimeric polypeptide structure (but not the carbohydrate) is important for binding of the hormone to specific receptors. The N‐linked but not O‐linked carbohydrates, on the other hand, are required in some manner to activate the effector system. Hormones with depleted carbohydrate content (deglycosylated hormones) interact with receptor but are unable to activate intracellular events. Because of such discordant properties, these forms act as competitive inhibitors of hormone action. Through a combination of chemical deglycosylation procedures and site‐directed mutagenesis, the first site of N‐glycosylation from the NH2terminus of the common α subunit has been identified to be most critical for glycoprotein hormone signal transduction. Control of glycosylation by the endocrine milieu could contribute to regulation of hormone function by secreting variable forms of agonist/antagonist.— Sairam, M. R. Role of carbohydrates in glycoprotein hormone signal transduction.FASEB J.3: 1915‐1926; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.8.2542111

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Of 600 carotenoids from natural sources that have been characterized, fewer than 10% serve as precursors of vitamin A. Many dietary carotenoids, both with and without provitamin A activity, are found in the blood and tissues of humans. β‐Carotene, the most nutritionally active carotenoid, comprises 15‐30% of total serum carotenoids. Vitamin A is formed primarily by the oxygen‐dependent central cleavage of β‐carotene and other provitamin A carotenoids. Several carotenoids show enhancement of the immune response, inhibition of mutagenesis, reduction of induced nuclear damage, and protection from various neoplastic events in cells, tissues, and whole animals. Carotenoids also protect against photo‐induced tissue damage. Some carotenoids, including β‐carotene, quench highly reactive singlet oxygen under certain conditions and can block free radical‐mediated reactions. In epidemiological studies, the intake of carotenoid‐rich fruits and vegetables has been correlated with protection from some forms of cancer, particularly lung cancer. Similarly, serum β‐carotene levels have been associated with a decreased chance of developing lung cancer. It must be stressed, however, that these epidemiological associations do not show cause and effect. In this regard, long‐term intervention trials with β‐carotene supplements are in progress. Whatever the results of these trials, carotenoids clearly show biological actions in animals distinct from their function as precursors of vitamin A.—Bendich, A.; Olson, J. A. Biological actions of carotenoids.FASEB J.3: 1927‐1932; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.8.2656356

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

The soluble proteins — or crystallins — that constitute the bulk of the cellular, transparent eye lens are encoded by a surprisingly diverse group of genes. Several crystallin genes generate further heterogeneity by producing more than one polypeptide, in which they use different mechanisms. Some crystallin genes are lens specific (e.g., αA and γ), while others show only lens preference (αB and enzyme/crystallins); all the crystallin genes are temporally and spatially regulated in the developing lens. Transfection and transgenic mouse experiments, identifying DNA regulatory elements in the 5' flanking region and in one case (δ) in an intron, point to transcriptional control as the primary basis for the tissue‐ and differentiation‐specific expression of crystallin genes. Crystallin promoters have been used to target foreign genes to the lens in transgenic and chimeric mice. Such gene transfer experiments have been used to create tumors and ablate specific cells in the lens. The identification of trans‐acting factors responsible for crystallin gene expression has begun but is in its infancy. The many mechanisms leading to the diversity and precise regulation of crystallins show that the lens is, in addition to a favorable tissue for studying differential gene expression, a fascinating portrait of molecular evolution.—Piatigorsky, J. Lens crystallins and their genes: diversity and tissue‐specific expression.FASEB J.3: 1933‐1940; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.8.2656357

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Novel eicosanoid biosynthetic pathways and receptors are reviewed as potential targets for pharmacological intervention. In addition to the cyclooxygenase and lipoxygenase pathways of arachidonate metabolism, a cytochrome P450‐dependent monooxygenase has been identified in corneal and renal epithelial cells. Elucidation of the enzymatic pathways of thromboxane (TX) disposition and development of analytical techniques for measuring urinary metabolites have allowed a reliable assessment of TXA2biosynthesis in health and disease, and provide a rationale for the combined use of TX‐synthase inhibitors and TXA2‐receptor antagonists in the setting of platelet activation. Recent evidence for a transcellular metabolism of neutrophilderived leukotriene (LT) A4by other human blood cells might link platelet and neutrophil activation to the occurrence of vasospastic phenomena. Prostacyclin (PG12), PGE2, PGD2, TXA2/PGH2, and sulfidopeptide‐LT receptors are being characterized in terms of distribution, signal‐transduction mechanisms, and agonist‐mediated regulation. Development of relatively selective agonists and antagonists of these receptors is providing novel therapeutic strategies for several human diseases.—Nicosia, S.; Patrono, C. Eicosanoid biosynthesis and action: novel opportunities for pharmacological intervention.FASEB J.3: 1941‐1948; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.8.2542112

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

In the present studies we examined the distribution, release, and biological actions of peptide tyrosine tyrosine (PYY) in the rat. The concentration and distribution of PYY was highest in the ileum and colon as determined by both radioimmunoassay of rat tissue extracts and immunocytochemistry. An ultrastructural comparison of rat and dog colonic PYY cells revealed a bipolar distribution of peptide‐containing secretory granules in both species. Serum PYY and pancreatic exocrine secretory responses were monitored after presentation of a meal to meal‐trained rats (n= 12). A significant increase in PYY concentrations was not observed until 120 min after meal presentation, a delayed response similar to that previously observed in the dog. PYY responses were also observed in rats after perfusion of the intestine at the level of the duodenum and ileum with an 80 mOsm micellar solution of sodium oleate. Duodenal instillations of the fatty acids resulted in a maximum PYY response after 120 min, whereas rats subject to ileal perfusion of fat exhibited maximum PYY release within the first hour. In other experiments, infusion of exogenous PYY at 100 pmol · kg−1· h−1, which reproduced plasma PYY levels observed after a meal and perfusion of the gut with fat, significantly inhibited CCK‐stimulated bile pancreatic volume (P<0.02), protein (P<0.01), and amylase (P<0.01) output. These studies demonstrate a bipolar distribution of PYY‐containing secretory granules in cells of the jejunal, ileal, and colonic mucosa, and show that PYY is released in response to a meal in amounts sufficient to inhibit cholecystokinin‐stimulated pancreatic secretion. Evidence is presented that PYY may mediate the delayed inhibition of pancreatic secretion that is observed in the rat after ingestion of a meal.—Aponte, G. W.; Park, K.; Hess, R.; Garcia, R.; Taylor, I. L. Meal‐induced peptide tyrosine tyrosine inhibition of pancreatic secretion in the rat.FASEB J.3: 1949‐1955; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.8.2721855

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

C57BL/6 mice bearing either a transplantable methylcholanthrene‐induced sarcoma or Lewis lung adenocarcinoma were passively immunized every other day with a rabbit immunoglobulin fraction raised against murine cachectin/tumor necrosis factor‐α. Mice bearing methylcholanthrene‐induced sarcoma developed tumor‐associated hypophagia that was attenuated by anticachectin immunoglobulin treatment. In the same tumor‐bearing animals, anticachectin treatment also significantly reduced the extent of carcass protein and fat loss, and reduced tumor weight. Mice bearing Lewis lung adenocarcinoma did not develop significant anorexia or carcass lean tissue depletion as tumor growth progressed, but they lost carcass lipid. Treatment of Lewis lung adenocarcinoma‐bearing mice with anticachectin antibodies diminished the degree of carcass lipid depletion and prevented plasma hypertriglyceridemia. However, in both tumor models, anti‐cachectin treatment did not affect either the development of anemia, hypoalbuminemia or the increase in serum amyloid P concentrations seen with increasing tumor burden. We conclude that an endogenous cachectin response, inhibitable by exogenously administered antibody, contributes to anorexia and to changes in body fat and protein metabolism in these tumor‐bearing animals. Neutralizing endogenous cachectin production with antibodies offers the potential to reduce tissue wasting that is frequently associated with neoplastic disease, but it does not appear to affect all of the hematologic and acute phase responses in these murine tumor models.— Sherry, B. A.; Gelin, J.; Fong, Y.; Marano, M.; Wei, H.; Cerami, A.; Lowry, S. F.; Lundholm, K. G.; Moldawer, L. L. Anticachectin/tumor necrosis factor‐α antibodies attenuate development of cachexin in tumor models.FASEB J.3: 1956‐1962; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.8.2721856

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Elementary Na+currents through single cardiac Na+channels were recorded at 19°C in patch clamp experiments with cultured neonatal rat cardiocytes. The metabolites of the glycolytic pathway, 2,3‐diphospho‐glycerate and glyceraldehyde phosphate, were identified as a novel class of modulators of Na+channel activity. In micromolar concentrations (1‐10 μmol/liter), their presence at the cytoplasmic membrane face increased the number of sequential openings during depolarization and prolonged the conductive channel state. As found after ensemble averaging, the decay kinetics of reconstructed macroscopic Na+currents became retarded and slow Na+inactivation may have been evoked. Both metabolites attenuated the rundown of channel activity that regularly develops after patch excision in the inside‐out patch configuration. It is tempting to assume that interference with Na+inactivation is the mode of action underlying the increase in single‐channel activity.—Kohlhardt, M., Fichtner, H.,andFröbe, U. Metabolites of the glycolytic pathway modulate the activity of single cardiac Na+channels.FASEB J.3: 1963‐1967; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.8.2542113

出版商:Wiley    

年代:1989

数据来源: WILEY