α-Endosulfine, a new entity in the control of insulin secretion

ATP-dependent potassium (K_ATP) channels occupy a key position in the control of insulin release from the pancreatic β cell since they couple cell polarity to metabolism. These channels close when more ATP is produced via glucose metabolism. They are also controlled by sulfonylureas, a class of drugs used in type 2 diabetic patients for triggering insulin secretion from β cells that have lost part of their sensitivity to glucose. We have demonstrated the existence of endogenous counterparts to sulfonylureas which we have called ‘endosulfines.’ In this review, we describe the discovery, isolation, cloning, and biological features of the high-molecular-mass form, α-endosulfine, and discuss its possible role in the physiology of the β cell as well as in pathology. Received 1 February 1999; received after revision 26 March 1999; accepted 26 March 1999     

Differential expression and dosage compensation of theα-amylase gene inDrosphila miranda

Summary The-amylase gene ofDrosophila miranda is located on the X²-and on the neo-Y-chromosome, both developing sex chromosomes. Crosses between strains carrying different electrophoretically distinguishable alleles of the-amylase gene were performed. Females of the F₁ offspring showed the expected heterozygosity, while the males proved to be hemizygous for this locus. Only the gene on the X²-chromosome is expressed, whereas the corresponding gene on the neo-Y-chromosome is not. Estimates of the-amylase activity in crude homogenates of male and female flies suggest strongly that the-amylase gene is dosage compensated inD. miranda. In contrast to this situation, in all otherDrosophila species the-amylase allele is autosomal and hence not dosage compensated.Acknowledgments. We would like to thank Betty C. Moore, for the kind supply ofD. miranda strains. For the help and advice in the electrophoretic separation of the-amylase variants we are indebted to Dr W. Pinsker. This work was supported by a grant from the Fonds zur Förderung der wissenschaftlichen Forschung, P5413 (Austria).     

The oxidative metabolism ofα-chlorohydrin and the chemical induction of spermatocoeles

Summary -Chlorohydrin (I) is oxidatively metabolized to -chlorolactic acid (III) and oxalic acid (IV). Deposition of calcium oxalate within the renal tubules is responsible for the toxic effects of-chlorohydrin and a similar action on the epididymis or epididymal blood vessels could initiate the formation of spermatocoeles from this and other male antifertility agents.     

Influence of the structure of theN-terminal extremity ofα-MSH on the melanophore stimulating activity of this hormone

Zusammenfassung Drei strukturelle Analoge des-MSH wurden synthetisiert und auf ihre Melanophoren-stimulierende Wirksamkeit untersucht. Für das Auftreten einer ausgeprägten biologischen Aktivität scheint die Anwesenheit einerN-Acetyl-Gruppe an dem Aminoende der Peptidkette wichtiger zu sein als das Vorhandensein der zwei ersten amino-endständigen Aminosäurereste der-MSH-Kette.     

α-1,3-Fucosyltransferase-VII stimulates the growth of hepatocarcinoma cells via the cyclin-dependent kinase inhibitor p27Kip1

After the transfection of -1,3-fucosyltransferase (FucT)-VII cDNA into H7721 human hepatocarcinoma cells, the protein expression of some cyclins, cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDIs) p16^INK4 and p21^waf1/Cip1 were unchanged. However, CDI p27^Kip1 protein, both the total amount and the amount that bound to CDK2, but not its mRNA, was significantly reduced. The de-inhibited CDK2 stimulated the phosphorylation of retinoblastoma (Rb) protein and facilitated the G1/S transition and growth rate of the cells. The decrease of p27^Kip1 protein, the increase of CDK2 activity and Rb phosphorylation, as well as the cell growth and percentage of S phase cells were correlated to the increased amount of cell surface sialyl Lewis X (SLe^x) antigen in cells with different -1,3-FucT-VII expression. The reduction in p27^Kip1 and the difference in its expression among different transfected cells were blocked by the SLe^x antibody KM93 in a dose-dependent manner, indicating that p27^Kip1 expression was influenced by -1,3-FucT-VII and its product SLe^x. The MEK/MAPK signaling pathway was more important than the PI-3K pathway in the regulation of p27^Kip1 expression.Received 5 August 2004; received after revision 25 October 2004; accepted 11 November 2005     

Elapidα-toxins have no effect on the cholinergic responses of bivalve myocardia

Summary Elapid-toxins (-bungarotoxin,-cobratoxin and crudeBungarus caeruleus venom) do not affect the myocardial nicotinic ACh receptors of the following bivalve molluscs:Mercenaria mercenaria, Chione cancellata, Mya arenaria, Mytilus edulis, Rangia cuneata andCrassostrea virginica.Acknowledgments. This work was supported by N.I.H. grant HL-09283 to M.J.G.; it is contribution No. 102 from the Tallahassee, Sopchoppy and Gulf Coast Marine Biological Association.     

Metabolism in porifera VI. Role of the 5,6 double bond and the fate of the C-4 of cholesterol during the conversion into 3β-hydroxymethyl-A-nor-5α-steranes in the spongeAxinella verrucosa

Summary During the conversion of cholesterol into 3 -hydroxymethyl-A-nor-5-cholestane by the spongeAxinella verrucosa, the carbon-3 of this latter originate from carbon-4 of cholesterol. Cholestanol moreover does not seem an intermediate in this conversion.     

α-Particle track autoradiographic study of the distribution of a [211At]-astatinated drug in normal tissues of the mouse

Summary The microscopic distribution of the potential endoradiotherapeutic drug, 6-[²¹¹At]-astato-2-methyl-1,4-naphthoquinol bis (diphosphate salt) in normal tissues of the mouse has been studied by -particle track autoradiography. The uptake into critical radiosensitive tissues, especially bone marrow, colon and lung, was low.     

Effect of radical scavengers on TNFα-mediated activation of the uPA in cultured cells

Active oxygen, produced by cultured cells following stimulation with various growth factors, seems to be involved in signal transduction leading to cellular responses such as gene expression and growth modulation. In the present study, the intracellular oxidation state was measured in immortalized human endothelial cells (ECV304) after treatment with tumor necrosis factor (TNF), using a fluorescent dye and a laser-scanning confocal microscope. The intracellular oxidation state was increased 60 min after the addition of TNF, and this increase was abolished by a radical scavenger, N-acetylcysteine (NAC), which is also a precursor of glutathione, and by pyrrolidine dithiocarbamate (PDTC). TNF increased the steady state level of urokinase-type plasminogen activator (uPA), and NAC inhibited this increase at a dose that also inhibited the increase in the intracellular oxidation state. PDTC, on the other hand, did not affect the induction of the uPA gene by TNF. These results suggest that intracellular glutathione level rather than the oxidation state is necessary for the induction of the uPA gene by TNF.     

Effect of tea consumption on the levels ofα-ketoglutarate and pyruvate dehydrogenase in rat brain

Summary Administration of tea to rats fed on a normal diet results in a marked drop in brain levels of total thiamine as well as of -ketoglutarate and pyruvate dehydrogenase activities. The patterns of decrease in both enzyme activities are similar to that of total thiamine content; they drop to about 65% of the control at 14–20 weeks after continuous consumption of tea.Supported by a grant from the International Foundation for Science (IFS), Sweden.     

Identification of 3α, 17α, 21-trihydroxy-5α-pregnane (allotetrahydro-17α-hydroxy-cortexone) and 3α,21-dihydroxy-5α-pregnane (allo-tetrahydro-cortexone) in human urine

Résumé Le 3, 17, 21-trihydroxy 5-pregnane (allo-tétrahydro-17-hydroxy-cortexone) et le 3,21-dihydroxy 5-prégane (allo-tétrahydro-cortexone) ont été identifiés dans l'urine humaine. Ces composés avaient les mêmes migrations chromatographiques avant ou après acétylation ou oxydation que les respectifs stéroïdes de synthèse.     

An in vitro kinetic study of the mixed inhibition of honeybee hemolymph PNP-α-D-glucosidase by sucrose

Summary Sucrose acts in vitro as a mixed inhibitor of (V+K+n) type towards honeybee hemolymph PNP--D-glucosidase activity. Between the stages of emergence and foraging, there is little change in the effect of the inhibitor on V_M (f_i=from 1.31 to 1.35 respectively) or n (f_i=from 1.09 to 1.07) but K is more markedly affected (f_i ^–1=from 1.17 to 1.87)^M. These observations reflect the decrease of K_i from 277 to 98 mM and of I₅₀ from 154 to 111 mM, but K_i scarcely alters during development (from 477 to 425 mM). These inhibitory effects of sucrose are intermediate between those previously reported for trehalose and glucose.Acknowledgments. Particular appreciation is due to Mrs C. Joliet for her meticulous technical assistance, and to Mr R. Paris for his care as beekeeper. Dr M.R.J. Morgan is grateful for financial support from The Leverhulme Trust. The Royal Society, I.C.I. Plant Protection and Shell International Petroleum.     

Kelletinin I and kelletinin A from the marine molluscBuccinulum corneum are inhibitors of eukaryotic DNA polymeraseα

Summary The inhibitory effect of esters of p-hydroxybenzoic acid (kelletinins I and A), extracted from the marine gastropodBuccinulum corneum, have been tested on eukaryotic and prokaryotic enzymes of DNA metabolism such as DNA polymerases and , DNA polymerase I, Exo III, pancreatic DNAse I, micrococcal DNAse andE. coli RNA polymerase. Kelletinin I and kelletinin A inhibit preferentially DNA polymerase. The inhibitory effect of kelletinin I involves the hydroxyl group of p-hydroxybenzoic acid.     

(Z,E)-α-farnesene,main constitutent of the hypertrophied Dufour's gland of the major workers ofPheidole pallidula (Formicidae)

Summary In the European dimorphic ant,Pheidole pallidula, the Dufour's gland of the major workers is hypertrophied and secretes nearly pure (Z, E)--farnesene. This compound is also present in the Dufour's gland of the minor workers but constitutes only around 10% of the volatiles. Chemical polymorphism inP. pallidula is different from that already reported for species ofPheidole from the New World.Aspirante au Fonds National de la Recherche Scientifique.Maître de recherches du Fonds National de la Recherche Scientifique.     

On the conformation of substituted cyclopentanones. Rotatory dispersion and spectral data of some steroidalα-halocyclopentanones

Zusammenfassung Die optische Rotationsdispersion sowie das Infrarotund Ultraviolett-Absorptionsspektrum von mehreren-Bromderivaten der 16-Keto- und 17-Ketosteroide wurde gemessen. Die Schlussfolgerungen aus Rotationsdispersion und Infrarotanalyse stimmen gut überein, es scheint jedoch, dass die Verschiebungen im Ultraviolett zur Bestimmung der Orientierung eines Halogenatoms in-Bromocyclopentanonen nicht in allen Fällen gebraucht werden können.

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Paper XXXV in the seriesOptical Rotatory Dispersion Studies by C. D. For the preceding article seeN. L. Allinger, R. B. Hermann, andC. Djerassi, J. org. Chem., in press.     

Hydrolysis of N-phenylacetyl-α-methyl-α-amino acids by benzylpenicillinacylase

Summary Enzymatic hydrolysis of several racemic N-phenylacetyl--methyl--amino acids containing an additinal aliphatic, aromatic or polar substitutent on the chiral carbon atom, has been studied by using benzylpenicillincylase fromEscherichia coli A.T.C.C. 9637. Both the rate of hydrolysis and the stereoselectivity were found to be considerably lower than in the case of natural -amino acids. Steric and electronic factors in the side chains influencing the stereoselectivity are discussed.     

Characterization of 17β-estradiol 3-(β-D-glucopyranoside) and 17-(α-D-glucopyranoside) as the metabolites of 17β-estradiol in the cultured ovaries of the silkworm,Bombyx mori

Summary The structures of the metabolites formed upon incubation of 17-estradiol with the ovaries of silkworm,Bombyx mori, have been determined as 17-estradiol 3-(-D-glucopyranoside) (1) and 17-(-D-glucopyranoside) (2) by spectroscopic means.     

Allosteric proteins after thirty years: The binding and state functions of the neuronalα7 nicotinic acetylcholine receptors

A key statement of the 1965 Monod-Wyman-Changeux (MWC) model for allosteric proteins concerns the distinction between the ligand-binding function ( ) and the relevant state function ( ). Sequential models predict overlapping behavior of the two functions. In contrast, a straightforward experimental consequence of the MWC model is that for an oligomeric protein the parameters which characterize the two functions should differ significantly. Two situations, where \bar Y$$ " align="middle" border="0"> and the system ishyper-responsive or where and the system ishypo-responsive, have been encountered. Indeed, the hyper-responsive pattern was first observed for the enzyme aspartate transcarbamoylase, by comparing with monitored by a change in sedimentation. Extensions of the theory to ligand-gated channels led to the suggestion that, on the one hand, hyper-responsive properties also occur with high-affinity mutants. On the other hand, native channels of the acetylcholine neuronal7 receptor and low-affinity mutants of the glycine receptor can be interpreted in terms of the hypo-responsive pattern. For the ligand-gated channels, whereas is detected directly by ion flux, ligand binding has rarely been measured and the formation of desensitized states may complicate the analysis. However, stochastic models incorporating both binding and channel opening for single molecules predict differences that should be measurable with new experimental approaches, particularly fluorescence correlation spectroscopy.