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PubMedDate not supplied

Protein:protein interactions in the lipid bilayer (review).

At least four different types of interaction between protein transmembrane helices have been described to date. These include the use of charge-pair interactions that can play a positive or negative role in the assembly of multi-subunit complexes such as the T cell receptor, or recruit signal transducing accessory molecules in the case of some Fc receptors. Inter-helix hydrogen bonds have been shown to play an important role in the constitutive activation of certain proto-oncogenes, whereas helix:helix interfaces stabilized solely by van der Waals contacts mediated by non-polar residues also exist. The fourth type of interaction is an inter-chain disulphide linkage which is dependent on a buried charged residue. A role for glycine residues in several of these mechanisms is also suggested. In addition, the use of disulphide mapping to further explore protein:protein interactions within the lipid bilayer is discussed.

Amino Acid Sequence↗
PubMed2006

Cyclin D1 antisense oligodexoyneucleotides inhibits growth and enhances chemosensitivity in gastric carcinoma cells.

AIM: To examine the effects of cyclin D1 antisense oligodexoyneucleotides (ASODN) on growth and chemosensitivity of gastric carcinoma cell lines SGC7901 and its mechanism. METHODS: Phosphorothioate modified cyclin D1 ASODN was encapsulated by LipofectAMINE2000 (LF2000) and transfected into cells, the dose-effect curves and growth curves were observed. 5-FU, MTX, CDDP of different concentrations were given after transfecting cells with cyclin D1 ASODN for 24 h the dose-effect responses were observed and IC50s were calculated. The mRNA expression of cyclin D1, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydrofolate reductase (DHFR) was detected by reverse transcription-PCR (RT-PCR) at 24 h and 48 h after transfection. RESULTS: Dose-dependent inhibitory effect was caused by cyclin D1 ASODN in SGC7901 cells. Transfecting gastric carcinoma cells with 0.2 micromol/L cyclin D1 ASODN for 24 h could inhibit growth significantly and reduce expression of cyclin D1 mRNA. Cyclin D1 ASODN could increase the chemosensitivity to 5-FU, MTX, CDDP in cells. The IC50s of different chemotherapeutic agents in ASODN plus chemotherapy groups were significantly lower than those in controls. Transfection with cyclin D1 ASODN leaded to an increase in TS and DHFR mRNA and a decrease in TP mRNA as determined by RT-PCR at 24 h, the alterations were more significant at 48 h. CONCLUSIONS: Cyclin D1 ASODN can decrease mRNA expression of cyclin D1, inhibit growth and enhance the chemosensitivity by changing the expression of enzymes related to metabolism of chemotherapeutic agents in SGC7901 gastric carcinoma cells.

Adenocarcinoma↗
PubMed1999

BDNF is a target-derived survival factor for arterial baroreceptor and chemoafferent primary sensory neurons.

Brain-derived neurotrophic factor (BDNF) supports survival of 50% of visceral afferent neurons in the nodose/petrosal sensory ganglion complex (NPG; Ernfors et al., 1994a; Jones et al., 1994; Conover et al., 1995; Liu et al., 1995; Erickson et al., 1996), including arterial chemoafferents that innervate the carotid body and are required for development of normal breathing (Erickson et al., 1996). However, the relationship between BDNF dependence of visceral afferents and the location and timing of BDNF expression in visceral tissues is unknown. The present study demonstrates that BDNF mRNA and protein are transiently expressed in NPG targets in the fetal cardiac outflow tract, including baroreceptor regions in the aortic arch, carotid sinus, and right subclavian artery, as well as in the carotid body. The period of BDNF expression corresponds to the onset of sensory innervation and to the time at which fetal NPG neurons are BDNF-dependent in vitro. Moreover, baroreceptor innervation is absent in newborn mice lacking BDNF. In addition to vascular targets, vascular afferents themselves express high levels of BDNF, both during and after the time they are BDNF-dependent. However, endogenous BDNF supports survival of fetal NPG neurons in vitro only under depolarizing conditions. Together, these data indicate two roles for BDNF during vascular afferent pathway development; initially, as a target-derived survival factor, and subsequently, as a signaling molecule produced by the afferents themselves. Furthermore, the fact that BDNF is required for survival of functionally distinct populations of vascular afferents demonstrates that trophic requirements of NPG neurons are not modality-specific but may instead be associated with innervation of particular organ systems.

Animals↗
PubMed2001

Increasing the number of synapses modifies olfactory perception in Drosophila.

The Drosophila mutant gigas produces an enlargement of postmitotic cells caused by additional rounds of DNA replication. In neurons, the mutant cell establishes more synapses than normal. We have taken advantage of this feature to study the effect of synapse number on odorant perception. Mosaic adults were generated in which one antenna was homozygous for gigas, whereas the contralateral side served as an internal control. Morphological analysis indicates that the number and type of sensory afferents forming the mutant antenna, as well as their projection to the olfactory glomeruli, are normal. In contrast, the volume of identified glomeruli increases to a variable extent, and mutant sensory neurons branch profusely. The number of synapses, estimated in the ventral (V) glomerulus that receives ipsilateral afferents only, is increased twofold to threefold. Large-dense-core vesicle-containing terminals that probably modulate olfactory centers are identified in the V glomerulus. Their number and size are not modified by the mutant input. Sensory transduction, measured by electroantennograms, is normal in amplitude and kinetics. In odorant tests, however, the profile of the behavioral response to ethyl acetate shows attractive responses to concentrations to which sibling controls remain indifferent (10(-)8 and 10(-)7 v/v). In addition, the intensity of the response is augmented both at attractive and repulsive odorant concentrations with respect to that of controls. These results demonstrate that increased synapse number in the sensory neurons can modify the behavior of the organism, allowing a higher sensitivity of perception.

Acetates↗
PubMed2004

Distribution of TRPC channels in a visceral sensory pathway.

Until recently most of the published studies addressing the mechanisms of activation of TRPC channels have been carried out in heterologous expression systems. Lack of specific antagonists for the TRPC channels has hampered functional studies of endogenous channels. We approached the role of TRPC channels in native tissue with a study of the distribution of the channel proteins in the carotid chemosensory pathway in the rat. In a previous report we showed that TRPC3/4/5/6 and TRPC7 were present in neurons throughout the petrosal ganglion while TRPC1 was expressed in only a subpopulation of petrosal neurons, at least half of which projected to the carotid body. The TRPC proteins were differentially distributed to the branches of the axons that project centrally to the nucleus of the solitary tract and peripherally to the carotid body. The smallest unmyelinated sensory fibres projecting to the carotid body contained TRPC1/3/4/5 or TRPC6 but not TRPC7. TRPC1 and TRPC3 were concentrated in the larger diameter fibres. Interestingly, only TRPC1 and TRPC4 could be demonstrated in the final terminal endings within glomus cell clusters of the carotid body. In the central axon of the sensory neurons, both TRPC4 and TRPC5 were demonstrated in fibres exiting the solitary tract and projecting to the secondary relay neurons the nucleus of the solitary tract.

Animals↗
PubMed1991

[Participation of calcium ions in carotid chemoreception].

The changes in calcium accumulation ability of glomus cells membranes under the action of alkaloids, acids and effector stimuli have been studied by fluorimetric chelate probe technique. The reception of these stimuli causes calcium-ions release mainly from the intracellular organoids membranes (mitochondrial and endoplasmatic). These data suggest that calcium-ions act as a messenger between extracellular stimuli and the metabolism of glomus cells. Results obtained provide the evidence of heterogeneity of carotid chemoreception mechanism.

Animals↗
PubMed1989

[The sensory cells of the fetal vomeronasal organ in the human. A contribution to the variability of their differentiation and rudimentary development].

Serial cranial sections of seven human fetuses between 11 and 18 weeks were studied using Palmgren's silver impregnation technique. The vomeronasal organ revealed receptor cells in four cases. This is the first demonstration of functional elements in the vomeronasal organ in man. They may also be present in old-world monkeys. It is evident that the human vomeronasal organ is frequently present in man, but differentiation of the organ and its individual constituents shows considerable variation.

Cell Differentiation↗
PubMed1985

Selective stabilization of retinotectal synapses by an activity-dependent mechanism.

How does each ingrowing retinal fiber select the right spot in the overall retinotopic projection? Chemospecific surface interactions appear to be sufficient only to organize a crude retinotopic map on the tectum during regeneration of the optic nerve of goldfish. Precise retinotopic ordering is achieved via an activity-dependent stabilization of appropriate synapses, based on the correlated activity of neighboring ganglion cells of the same receptive field type in the retina. Four treatments have been found to block the sharpening process: 1) blocking activity of the ganglion cells with intraocular tetrodotoxin (TTX); 2) rearing in total darkness; 3) correlated activation of all ganglion cells via stroboscopic illumination in a featureless environment; 4) block of retinotectal synaptic transmission with alpha-bungarotoxin. These experiments support a role for normal visually driven activity in sharpening the diffuse projection, and demonstrate that the correlated activity of the optic fibers interacts within the postsynaptic cells, probably through the summation of excitatory postsynaptic potentials. Intraocular TTX experiments suggest that a similar mechanism may drive both the formation of ocular dominance patches in fish tectum and kitten visual cortex and the segregation of different receptive field types in the lateral geniculate nucleus. Thus, it may be a general mechanism whereby the diffuse projections of early development are brought to a mature level of organization.

Bungarotoxins↗