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71.
Le Nevé B Foltz M Daniel H Gouka R 《American journal of physiology. Gastrointestinal and liver physiology》2010,299(6):G1368-G1375
Steroid glycosides extracted from the succulent plant Hoodia gordonii are suggested to have appetite-suppressant effects both in animals and humans. Yet, the mechanisms underlying the putative satiety action of Hoodia steroid glycosides are not fully understood. We found that H.g.-12, a steroid glycoside purified from H. gordonii extract, initiated cholecystokinin (CCK) secretion both ex vivo in rat intestine and in vitro in the human enteroendocrine (EC) cell line HuTu-80. CCK is known to exert central effects on appetite suppression via the vagus nerve which afferents terminate in the gut wall. Recent data show that G protein-coupled receptors signaling bitter taste (T2Rs) are expressed in both rodent and human gastrointestinal tract. It was further demonstrated that bitter sensing is functional in mouse STC-1 EC cells and leads to CCK secretion via increased intracellular Ca2(+) concentrations. Based on the bitter taste of H. gordonii purified extracts, we assessed whether H.g.-12 could activate human bitter receptors. The steroid glycoside activated selectively TAS2R7 and TAS2R14, both heterologously expressed in HEK 293 cells. Removing an essential structural feature from the steroid glycoside inhibited H.g.-12-induced Ca2(+) increase in TAS2R14-expressing HEK cells and abolished H.g.-12-induced CCK secretion from human EC cells. Similarly, a nonspecific bitter receptor antagonist abolished H.g.-12-induced CCK secretion in HuTu-80 cells. These results point to a potential route of action by which components of Hoodia might influence appetite control. Our data also provide additional evidence that bitter taste-sensing mechanisms are coupled to hormone release from EC cells in the intestine. Moreover, we identified a natural agonist of TAS2R7 and TAS2R14 for further studies on the role of bitter receptors in satiety control and food intake. 相似文献
72.
Ancient, long-extinct floras and faunas can be reassembled through fossils and phylogenetics, and even palaeo-environments can be reconstructed with the aid of palaeoclimatology. However, very little is known about the sound-scape of the past. Of what kind were the first biologically meaningful sounds and vibrations ever emitted and perceived? The earliest signals in the history of life were probably produced by arthropods making use of the mechanical properties of their exoskeleton. Here, we report an observation of vibrational signalling in the coleorrhynchan Hackeriella veitchi, a representative of a Gondwanan relict insect lineage which is still extant in the Queensland rainforest. Our finding suggests that vibrational signalling by tymbal organs is ancestral for the Hemiptera (exclusive of Sternorrhyncha)--the song of the Coleorrhyncha was a likely element of the acoustic environment in the Permian moss forests and had possibly changed little since. 相似文献
73.
Alvarez J Hamplova J Hohaus A Morano I Haase H Vassort G 《The Journal of biological chemistry》2004,279(13):12456-12461
Ahnak, a protein of 5643 amino acids, interacts with the regulatory beta-subunit of cardiac calcium channels and with F-actin. Recently, we defined the binding sites among the protein partners in the carboxyl-terminal domain of ahnak. Here we further narrowed down the beta(2)-interaction sites to the carboxyl-terminal 188 amino acids of ahnak by the recombinant ahnak protein fragments P3 (amino acids 5456-5556) and P4 (amino acids 5556-5643). The effects of these P3 and P4 fragments on the calcium current were investigated under whole-cell patch clamp conditions on rat ventricular cardiomyocytes. P4 but not P3 increased significantly the current amplitude by 22.7 +/- 5% without affecting its voltage dependence. The slow component of calcium current inactivation was slowed down by both P3 and P4, whereas only P3 slowed significantly the fast one. The composite recombinant protein fragment P3-P4 induced similar modifications to the ones induced by each of the ahnak fragments. In the presence of carboxyl-terminal ahnak protein fragments, isoprenaline induced a similar relative increase in current amplitude and shift in current kinetics. The actin-stabilizing agents, phalloidin and jasplakinolide, did not modify the effects of these ahnak protein fragments on calcium current in control conditions nor in the presence of isoprenaline. Hence, our results suggest that the functional effects of P3, P4, and P3-P4 on calcium current are mediated by targeting the ahnak-beta(2)-subunit interaction rather than by targeting the ahnak-F-actin interaction. More specifically they suggest that binding of the beta(2)-subunit to the endogenous subsarcolemmal giant ahnak protein re-primes the alpha(1C)/beta(2)-subunit interaction and that the ahnak-derived proteins relieve the beta(2)-subunit from this inhibition. 相似文献
74.
Wetzel K Baltatu O Nafz B Persson PB Haase H Morano I 《American journal of physiology. Regulatory, integrative and comparative physiology》2003,284(2):R607-R610
We demonstrated recently a significantly lower fraction of cardiac precapillary arterioles that expressed smooth muscle myosin heavy chain (MyHC) B (SMB) in spontaneously hypertensive rats. To clarify whether this reduction of SMB expression is of genetic origin, we investigated SMB expression in cardiac precapillary arterioles of normotensive and experimentally hypertensive rats (one clip, one kidney or ANG II minipump). We observed similar SMB expression patterns in precapillary arterioles of experimentally hypertensive rats compared with normotensive controls. These observations suggest that the downregulation of SMB in spontaneously hypertensive rats is of genetic origin rather than an adaptive response to chronically enhanced blood pressure and cardiac hypertrophy. 相似文献
75.
We recently cloned and functionally characterized two novel proton/amino acid transporters (PAT1 and PAT2) from mouse. Here we report the isolation of the corresponding cDNAs of the human orthologues and one additional mouse and human PAT-like transporter cDNA, designated PAT3. The PAT proteins comprise 470 to 483 amino acids. The mouse PAT3 mRNA is expressed in testis of adult mice. In the human and mouse genomes the genes of the PAT transporters (designated SLC36A1-3 and Slc36a1-3, respectively) are clustered on human chromosome 5q33.1 and in the syntenic region of mouse chromosome 11B1.3. PAT-like transporter genes are present as well in the genomes of other eukaryotic organisms such as Drosophila melanogaster and Caenorhabditis elegans. For the PAT3 subtype transporter, we could not yet identify its function. The human PAT1 and PAT2 transporters when functionally expressed in Xenopus laevis oocytes show characteristics similar to those of their mouse counterparts. 相似文献
76.
Brandt H Hauert C Sigmund K 《Proceedings. Biological sciences / The Royal Society》2003,270(1519):1099-1104
The puzzle of the emergence of cooperation between unrelated individuals is shared across diverse fields of behavioural sciences and economics. In this article we combine the public goods game originating in economics with evolutionary approaches traditionally used in biology. Instead of pairwise encounters, we consider the more complex case of groups of three interacting individuals. We show that territoriality is capable of promoting cooperative behaviour, as in the case of the Prisoner's Dilemma. Moreover, by adding punishment opportunities, the readiness to cooperate is greatly enhanced and asocial strategies can be largely suppressed. Finally, as soon as players carry a reputation for being willing or unwilling to punish, highly cooperative and fair outcomes are achieved. This group-beneficial result is obtained, intriguingly, by making individuals more likely to exploit their co-players if they can get away with it. Thus, less-cooperative individuals make more-cooperative societies. 相似文献
77.
Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains 总被引:5,自引:0,他引:5
Swinnen JV Van Veldhoven PP Timmermans L De Schrijver E Brusselmans K Vanderhoydonc F Van de Sande T Heemers H Heyns W Verhoeven G 《Biochemical and biophysical research communications》2003,302(4):898-903
Fatty acid synthase (FAS) is a key metabolic enzyme catalyzing the synthesis of long-chain saturated fatty acids. It plays a central role in the production of surfactant in fetal lungs, in the supply of fatty components of milk, and in the conversion and storage of energy in liver and adipose tissue. Remarkably high levels of FAS expression are found in the majority of human epithelial cancers. As the role of FAS in cancer cells remains largely unknown, we have initiated studies to assess the fate of newly synthesized lipids in cancer cells and have estimated the contribution of FAS to the synthesis of specific lipid classes by treating the cells with small interfering RNAs targeting FAS. Here, we show that in cancer cells FAS plays a major role in the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains. These are raft-aggregates implicated in key cellular processes including signal transduction, intracellular trafficking, cell polarization, and cell migration. These findings reveal a novel role for FAS, provide important new insights into the otherwise poorly understood mechanisms underlying the control of lipid composition of membrane microdomains, and point to a link between FAS overexpression and dysregulation of membrane composition and functioning in tumor cells. 相似文献
78.
Serikov V Bodi I Koch SE Muth JN Mikala G Martinov SG Haase H Schwartz A 《Biochemical and biophysical research communications》2002,293(5):1405-1411
The beta subunit of the L-type voltage-dependent calcium channel modifies the properties of the channel complex by both allosteric modulation of the alpha1 subunit function and by chaperoning the translocation of the alpha1 subunit to the plasma membrane. The goal of this study was to investigate the functional effect of changing the in vivo stoichiometry between the alpha1 and beta subunits by creating a dominant negative expression system in a transgenic mouse model. The high affinity beta subunit-binding domain of the alpha1 subunit was overexpressed in a cardiac-specific manner to act as a beta subunit trap. We found that the predominant beta isoform was located primarily in the membrane bound fraction of heart protein, whereas the beta1 and beta3 were mostly cytosolic. There was a significant diminution of the amount of beta2 in the membrane fraction of the transgenic animals, resulting in a decrease in contractility of the heart and a decrease in L-type calcium current density in the myocyte. However, there were no distinguishable differences in beta1 and beta3 protein expression levels in the membrane bound fraction between transgenic and non-transgenic animals. Since the beta1 and beta3 isoforms only make up a small portion of the total beta subunit in the heart, slight changes in this fraction are not detectable using Western analysis. In contrast, beta1 and beta3 in skeletal muscle and brain, the predominant isoforms in these tissues, respectively, are membrane bound. 相似文献
79.
Niels Jensen Martin Hasselblatt Anna-Leena Sirén Lothar Schilling †Martin Schmidt Hannelore Ehrenreich 《Journal of neurochemistry》1998,70(2):473-482
Abstract: Using a whole-cell binding procedure with long incubations at low temperature and subsequent acid stripping, we have characterized an atypical endothelin (ET) receptor in primary rat cortical astrocyte cultures. We found the following: (a) no competition for 125 I-ET-1 binding by the ETA antagonists BQ-123 and LU 135252 or the ETB agonist IRL 1620; (b) weak competition by the ETB antagonist BQ-788 and by the predominant ETB ligand ET-3; (c) potent synergistic competition of ETA and ETB ligands in combination for 125 I-ET-1 binding; (d) potent competition of ET-1 with any of the radioligands used, 125 I-ET-1, 125 I-IRL 1620, and [3 H]BQ-123; (e) lack of competition of IRL 1620 and BQ-123 with the respective other radioligand; (f) shifting of the amount of acid-strippable 125 I-ET-1 binding from 20 to 80% by ETB ligands and to 4% by ETA ligands; and (g) as a control, typical ETA and ETB binding characteristics of the RAT-1 fibroblast and the U373MG astrocytoma cell line, respectively, under our assay conditions. The unusual binding properties of astrocytic ET receptors described in this study appear to be the result of several binding sites in the receptor for different ET ligands or ligand epitopes. 相似文献
80.