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641.
Preparation of a pure monoiodo derivative of the bee venom neurotoxin apamin and its binding properties to rat brain synaptosomes 总被引:5,自引:0,他引:5
M Hugues D Duval P Kitabgi M Lazdunski J P Vincent 《The Journal of biological chemistry》1982,257(6):2762-2769
The preparation and purification of an active monoiodo derivative of apamin is described. Radiolabeled monoiodoapamin (2000 Ci/mmol) binds specifically to rat brain synaptosomes at 0 degrees C and pH 7.5 with a second order rate constant of association (ka = 2.6 x 10(7) M-1 s-1) and a first order rate constant of dissociation (kd = 3.8 x 10(-4) s-1). The maximal binding capacity is 12.5 fmol/mg of protein and the dissociation constant is 15-25 pM for the monoiodo derivative and 10 pM for the native toxin. The apamin receptor is destroyed by proteases suggesting that it is of a proteic nature. Neurotensin and its COOH-terminal partial sequences are the only molecules unrelated to apamin that are able to displace monoiodoapamin from its receptor at low concentrations. Half-displacement occurs at 170 nM neurotensin. This property is due to the presence in the COOH-terminal sequence of neurotensin of two contiguous arginine residues, a structure analogous to that of the apamin active site. The binding of monoiodoapamin to its receptor is sensitive to cations. Increasing K+ or Rb+ concentrations from 10 microM to 5 mM selectively enhances the binding by a factor of 1.8. Increasing the concentration of any cation from 1 to 100 mM completely inhibits iodoapamin binding. Both effects are due to a cation-induced modulation of the affinity of monoidoapamin for its receptor without any change of the maximal toxin binding capacity of synaptosomes. Guanidinium and molecules containing a guanidinium group are better inhibitors of iodoapamin binding than other inorganic cations or positively charged organic molecules. 相似文献
642.
Identification of a protein component of the Ca2+-dependent K+ channel by affinity labelling with apamin 总被引:2,自引:0,他引:2
M Hugues H Schmid M Lazdunski 《Biochemical and biophysical research communications》1982,107(4):1577-1582
The red blood cell membrane proteins and plasma proteins of normal and spontaneously hypertensive rats were studied by uni- and bidimensional polyacrylamide gel electrophoresis. The amount of band 3, the major intrinsic protein of the erythrocyte membrane, was observed to be significantly reduced in spontaneously hypertensive rats. Plasma from these rats contained two additional heat stable proteins, characterized by a molecular weight of 16,000 daltons and isoelectric points of 4.7 and 5.1, respectively. These proteins were not detected in normotensive control Wistar Kyoto rats, in normal Wistar rats, or in Wistar rats with experimentally induced hypertension. 相似文献
643.
Dominique Crenesse Ghislaine Neuilly Jean Gugenheim Catherine Ferre Michel Hugues 《European journal of biochemistry》2003,270(9):1952-1957
Post ischaemic cell calcium invasion has been described as one of the main causes of graft failure. Protective effects of calcium antagonists have been investigated but are not convincing and their mechanisms of action remain unclear. In this work we tested the protective effect of a new calcium inhibitor described to block a calcium current insensitive to all known calcium blockers. Specific mapacalcine receptors were first characterized on rat hepatocytes membranes using the 125I-labeled mapacalcine. 45Ca fluxes were then measured on cultured hepatocytes submitted (or not) to an hypoxic period. The action of mapacalcine was investigated on the ischaemia-induced calcium influx. We demonstrate here that: (a) there are specific receptors for mapacalcine in rat hepatocytes; (b) Mapacalcine is able to specifically block ischaemia-induced calcium influx with an IC50 of 0.3 micro m and does not significantly interact with the basal calcium flux. Our work demonstrates that the mapacalcine receptor is a cellular structure directly involved in the phenomenon of postischaemic cell invasion by calcium. Specific block of ischaemia-induced Ca2+ influx by mapacalcine suggests that the development of a panel of pharmacological drugs acting on this receptor could lead to the discovery of therapeutic agents able to protect cells against one of the events responsible for organ failure after transplantation or simply after an ischaemic period. Moreover, identification of the cellular protein which binds mapacalcine may become an important step in the research of mechanisms involved in postischaemic cell invasion by calcium. 相似文献
644.
The cytotoxicity of both methotrexate (MTX) and methotrexate-poly(L-lysine) conjugate (MTX-poly(lys)) on L929 mouse fibroblasts can be prevented by the simultaneous administration of Leucovorin. Thiamine pyrophosphate, an inhibitor for MTX-transport, protects cells from the toxicity of MTX, but not of MTX-poly(lys). Heparin at low concentration (1 μg/m1) completely abolishes the toxic effect of MTX-poly(lys), but not of MTX. These results suggest that although MTX and MTX-poly(lys) share the same mode of drug action inside the cell, they possess completely different transport mechanisms at the cell surface. The protection of cells by heparin against MTX-poly(lys) is biphasic, i.e. at higher heparin concentration (>10 μg/m1) the cytotoxicity can be partially restored. This observation suggests that this polyanion may have cellular effects other than neutralizing the positive charges on the drug carrier poly(lysine). 相似文献
645.
Martin Hagedorn Maylis Delugin Isabelle Abraldes Nathalie Allain Marc-Antoine Belaud-Rotureau Michelle Turmo Claude Prigent Hugues Loiseau Andréas Bikfalvi Sophie Javerzat 《Cell division》2007,2(1):1-12
Ubiquitin is a highly versatile post-translational modification that controls virtually all types of cellular events. Over the past ten years we have learned that diverse forms of ubiquitin modifications and of ubiquitin binding modules co-exist in the cell, giving rise to complex networks of protein:protein interactions. A central problem that continues to puzzle ubiquitinologists is how cells translate this myriad of stimuli into highly specific responses. This is a classical signalling problem. Here, we draw parallels with the phosphorylation signalling pathway and we discuss the expanding repertoire of ubiquitin signals, signal tranducers and signalling-regulated E3 enzymes. We examine recent advances in the field, including a new mechanism of regulation of E3 ligases that relies on ubiquitination. 相似文献
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648.
Evidence for the presence of β-subunit of hexosaminidase in a case of Sandhoff disease using a blotting technique 总被引:1,自引:0,他引:1
Sophie Gautron Livia Poenaru Joëlle Boue Hugues Puissant Jan J. W. Lisman Jean-Claude Dreyfus 《Human genetics》1983,63(3):258-261
Hexosaminidases, lysosomal enzymes whose deficiency is responsible for several genetic disorders, exist as two major forms: form A, containing two types of subunits alpha and beta; and form B, containing only beta subunits. We have used a technique involving successively electrophoresis of denatured proteins, transfer (blotting) onto nitrocellulose, and labelling by appropriate antibodies raised against the dissociated forms of hexosaminidases A and B. This technique allows the detection of alpha and beta subunits in crude extracts of normal tissues. The presence of beta chains was demonstrated in the liver of a fetus affected with Sandhoff's disease, deficient in functional hexosaminidases A and B. 相似文献
649.