Biomedical subjects

S Q Liu

Publications and source records attributed to S Q Liu.

At least 19 recordsLinked to original sources

PubMed2006

Acaricidal activities of extracts of Kochia scoparia against Tetranychus urticae, Tetranychus cinnabarinus, and Tetranychus viennensis (Acari: Tetranychidae).

Extracts of an annual herbaceous plant, Kochia scoparia (L.) Schrad (Macrophomina), were bioassayed to determine their acaricidal activities against Tetranychus urticae Koch, Tetranychus cinnabarinus (Boisduval), and Tetranychus viennensis Zacher (Acari: Tetranychidae) in the laboratory. Extracts had both contact and systemic toxicity to these mites. Three solvents were tested for preparing crude extracts: petroleum ether, chloroform, and methanol. Methanol was the most effective solvent, extracting 3.11-4.53% of the acaricide. Petroleum ether was the least effective solvent, extracting 1.25-1.54%. However, extracts with chloroform resulted in the highest mite mortality (78.86%), and ultrasound-assisted extraction required the least time (10 min). Concentrated extracts were prepared using chloroform, methyl acetate, or distilled water as a solvent. Mite mortalities from the concentrated extracts by methyl acetate or distilled water were significantly lower than those by chloroform. The mean lethal concentrations (LC50) of the extracts by chloroform, methyl acetate, and distilled water to the mites were 0.71 +/- 0.06, 2.08 +/- 0.16 and 8.75 +/- 0.062 mg/ml, respectively. After liquid chromatography and thin layer chromatography, the concentrated extracts by chloroform were separated into seven groups of isolated fractions and tested for acaricidal activity.

Animals↗

PubMed2005

Thermally sensitive micelles self-assembled from poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(D,L-lactide-co-glycolide) for controlled delivery of paclitaxel.

Thermally sensitive micelles self-assembled from poly(N-isopropylacrylamide-co- N,N-dimethylacrylamide)-b-poly(d,l-lactide-co-glycolide)[P(NIPAAm-co-DMAAm)-b-PLGA] are fabricated and used as a carrier for the controlled delivery of paclitaxel. Paclitaxel is efficiently loaded into the micelles by a membrane dialysis method. The lower critical solution temperature (LCST) of the micelles is 39.0 degrees C in PBS. Encapsulation efficiency and loading level of paclitaxel are affected by the initial loading level of paclitaxel, fabrication temperature and polymer composition. The blank and paclitaxel-loaded micelles are characterized by particle size analysis (DLS), morphology (TEM and AFM) and paclitaxel distribution (NMR, DSC and WAXRD). The micelles are spherical in shape, having an average size less than 130 nm. Paclitaxel is molecularly distributed within the core of micelles. Sustained release of paclitaxel is achieved, which is much faster at a temperature above the LCST than at the normal body temperature (37 degrees C). Cytotoxicity of free paclitaxel and paclitaxel-loaded micelles against a human breast carcinoma cell line (MDA-MB-435S) is studied at different temperatures. The cytotoxicity of the paclitaxol-loaded micelles is greater as compared to free paclitaxel. Enhanced cytotoxicity is achieved by the paclitaxol-loaded micelles when the environmental temperature increases slightly above the LCST. Paclitaxel-loaded P(NIPAAm-co-DMAAm)-b-PLGA micelles may provide a good formulation for cancer therapy.

Acrylamides↗

PubMed2005

Incorporation and in vitro release of doxorubicin in thermally sensitive micelles made from poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(D,L-lactide-co-glycolide) with varying compositions.

Thermally sensitive block copolymers, poly(N-isopropylacrylamide-co-N, N-dimethylacrylamide)-b-poly(d,l-lactide-co-glycolide) [P(NIPAAm-co-DMAAm)-b-poly(D,L-lactide-co-glycolide) (PLGA)] with different compositions and lengths of PLGA block are synthesized and utilized to fabricate micelles containing doxorubicin (DOX), a model anticancer drug, by a membrane dialysis method for targeted anticancer drug delivery. The critical association concentration (CAC) of the polymers ranges from 4.0 to 25.0 mg/L. An increased length of core-forming block PLGA leads to a decrease in the CAC. The clearly defined core-shell structure of micelles is proved by 1H-NMR analyses of the micelles in CDCl3 and D2O. The morphology of the micelles is analyzed by transmission electron microscopy, showing a spherical structure of both blank and drug-loaded micelles. The results obtained from dynamic light scattering show that the blank and drug-loaded micelles have an average size below 200 nm. The lower critical solution temperature (LCST) of the micelles made from the various polymers is similar, around 39 degrees C in phophate-buffered solution (PBS). The presence of serum in PBS does not alter the LCST significantly. The drug loading capacity varies depending on the PLGA block. The polymers are degradable, and the degradation of PLGA-based polymers is faster than that of poly(lactide) (PLA)-based polymer. The DOX-loaded micelles are stable in PBS containing serum at 37 degrees C but deform at 39.5 degrees C above the normal body temperature, thus triggering DOX release. It is revealed by confocal laser scanning microscopy that free DOX molecules enter cell nuclei very fast and DOX-loaded micelles accumulate mostly in cytoplasm after endocytosis. At a temperature above the LCST, more DOX molecules release from the micelles and enter the nuclei as compared to the temperature below the LCST. DOX-loaded micelles show greater cytotoxicity at a temperature above the LCST. The P(NIPAAm-co-DMAAm)-b-PLGA micelles developed may be a good carrier for anticancer drug delivery.

Acrylamides↗

PubMed2005

Microwave tumour coagulation plus in situ treatment with cytokine-microparticles: induction of potent anti-residual tumour immunity.

After local microwave coagulation and subsequent intra-tumoural injection of microparticles encapsulating interleukin-2 and granulocyte-macrophage colony-stimulating factor, the anti-tumour efficacy against subcutaneous Lewis lung carcinoma in syngeneic mice was evaluated. This treatment elicited a potent systemic anti-tumour immunity that protected treated mice from re-challenge with the same tumour cells and caused the distal tumours in a bilateral tumour model to be rejected. Cytotoxicity assay indicated that both T- and natural killer cells acted as the effector cells in the anti-tumour immunity. These data highlight the feasibility of microwave-pre-treated in situ cancer vaccination for clinical use.

Animals↗

PubMed2004

Acaricidal activities of extracts of Stellera chamaejasme against Tetranychus viennensis (Acari: Tetranychidae).

Extracts of a perennial and poisonous weed, Stellera chamaejasme L. (Thymelaeaceae) were bioassayed to determine their acaricidal activities against Tetranychus viennensis Zacher (Acari: Tetranychidae) in the laboratory. Extracts had both contact and systemic toxicity to the mite. After liquid chromatography and thin layer chromatography, the extract was further concentrated, separated, and bioassayed. This study is the first to report the acaricidal property of S. chamaejasme and its potential as a botanical pest control agent.

Insecticides↗

PubMed2002

A possible role of initial cell death due to mechanical stretch in the regulation of subsequent cell proliferation in experimental vein grafts.

The proliferation of vascular cells contributes to the formation of neointima and hypertrophy of the blood vessel wall. Here we show that mechanical stretch possibly regulates the proliferation of vascular cells via the mediation of cell death in a rat vein graft model. The wall of vein grafts is subject to a suddenly increased mechanical stretch due to exposure to arterial blood pressure. Such a stretch induces rapid cell death with a reduction in cell density by approximately 60% within the first day after surgery. The initial cell death was followed by an increase in the percentage of proliferating cells, as shown by a BrdU incorporation assay (1.55 +/- 1.27%, 8.48 +/- 2.27%, 11.93 +/- 2.36%, 6.36 +/- 1.77%, and 5.60 +/- 1.46% at days 1, 5, 10, 20, and 30, respectively). When mechanical stretch was reduced by restraining the vein graft using a polytetrafluoroethylene sheath, the percentage of proliferating cells reduced significantly (0.76 +/- 0.76%, 1.70 +/- 0.46%, 1.29 +/- 0.56%, 0.99 +/- 0.83%, and 0.47+/-0.52% at days 1, 5, 10, 20, and 30, respectively). A further reduction in cell density, induced by local administration of a cell death inducer ceramide to experimental vein grafts (without sheath), enhanced subsequent cell proliferation. In contrast, a prevention of cell death, induced by local administration of a cell death inhibitor tetrapeptide-aldehyde DEVD-CHO to experimental vein grafts (without sheath), significantly reduced subsequent cell proliferation. These results suggest that mechanical stretch induces cell death, which possibly mediates subsequent cell proliferation in the present model.

Adaptation, Physiological↗

PubMed2002

Control of the shape of a thrombus-neointima-like structure by blood shear stress.

Fluid mechanical factors are thought to influence vascular morphogenesis. Here we show how blood shear stress regulates the shape of a thrombus-neointima-like tissue on a polymer micro-cylinder implanted in the center of the rat vena cava with the micro-cylinder perpendicular to blood flow. In this model, the micro-cylinder is exposed to a laminarflow with a known shear stress field in the leading region and a vortexflow in the trailing region. At 1, 5, 10, 20, and 30 days after implantation, it was found that the micro-cylinder was encapsulated by a thrombus-neointima-like tissue with a streamlined body profile. The highest growth rate of the thrombus-neointima-like tissue was found along the trailing and leading stagnation edges of the micro-cylinder. Blood shear stress in the laminar flow region was inversely correlated with the rate of thrombus formation and cell proliferation, and the percentage of smooth muscle a actin-positive cells. These biological changes were also found in the trailing vortex flow region, which was associated with lowered shear stress. These results suggest that blood shear stress regulates the rate of thrombus and neointimal formation and, thus, influences the shape of the thrombus-neointima-like structure in the present model.

Actins↗

PubMed2002

[Inhibition of telomerase activity by ribozyme targeted to human telomerase transcriptase].

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit and the key factor which controls the telomerase activity,so it is the best choice to inhibit telomerase through controling hTERT expression.In this work,a hammer head ribozyme directed against the hTERT mRNA (hTERTRZ) was designed and synthesized to serve as a telomerase inhibitor. In order to test its in vitro cleavage activity, two in vitro transcription plasmids containing hTERTRZ and hTERT gene respectively were constructed. Ribozyme RNA and DIG-labeled-hTERT were synthesized by in vitro transcription. In vitro cleavage reactions were carried out by mixing the hTERTRZ with DIG-labeled-hTERT under different reaction conditions, and cleavage bands were detected by digoxin chemiluminescent assay. hTERTRZ showed a specific cleavage activity against the hTERT used as template. To investigate its in vivo effect of telomerase inhibition in tumor cells, a eukaryotic expression plasmid containing the hTERT ribozyme gene was introduced into HeLa cells and hepatoma cells by using LipofectAMINE. In the transfectants, the level of intact hTERT mRNA and the telomerase activity were clearly reduced, and the telomere length of these clones was apparently shortened at the beginning period, then kept a fixed value without further shortening. All the transfectants with ribozyme grew clearly more slowly than the parental cell line. The doubling time of the tansfectants prolonged compared to the negative control, but no apparent apoptosis was shown even at their 37th passage. These findings suggest the potential application of this ribozyme as a new theraputic agent directed against immortalized cancer cells.

DNA-Binding Proteins↗

PubMed2001

Binding of pyridine coenzymes to the beta-subunit of the voltage sensitive potassium channels.

The beta-subunit of the voltage-sensitive K(+) channels shares 15-30% amino acid identity with the sequences of aldo-keto reductases (AKR) genes. However, the AKR properties of the protein remain unknown. To begin to understand its oxidoreductase properties, we examine the pyridine coenzyme binding activity of the protein in vitro. The cDNA of K(v)beta2.1 from rat brain was subcloned into a prokaryotic expression vector and overexpressed in Escherichia coli. The purified protein was tetrameric in solution as determined by size exclusion chromatography. The protein displayed high affinity binding to NADPH as determined by fluorometric titration. The K(D) values for NADPH of the full-length wild-type protein and the N-terminus deleted protein were 0.1+/-0.007 and 0.05+/-0.006 M, respectively - indicating that the cofactor binding domain is restricted to the C-terminus, and is not drastically affected by the absence of the N-terminus amino acids, which form the ball and chain regulating voltage-dependent inactivation of the alpha-subunit. The protein displayed poor affinity for other coenzymes and the corresponding values of the K(D) for NADH and NAD were between 1-3 microM whereas the K(D) for FAD was >10 microM. However, relatively high affinity binding was observed with 3-acetyl pyridine NADP, indicating selective recognition of the 2' phosphate at the binding site. The selectivity of K(v)beta2.1 for NADPH over NADP may be significant in regulating the K(+) channels as a function of the cellular redox state.

Animals↗

PubMed2001

Involvement of aldose reductase in the metabolism of atherogenic aldehydes.

Phospholipid peroxidation generates a variety of aldehydes, which includes free saturated and unsaturated aldehydes, and aldehydes that remain esterified to the phosphoglyceride backbone - the so-called 'core' aldehydes. However, little is known in regarding the vascular metabolism of these aldehydes. To identify biochemical pathways that metabolize free aldehydes, we examined the metabolism of 4-hydroxy-trans-2-nonenal in human aortic endothelial cells. Incubation of these cells with [3H]-HNE led to the generation of four main metabolites, i.e. glutathionyl HNE (GS-HNE), glutathionyl dihydroxynonene (GS-DHN), DHN and 4-hydroxynonanoic acid (HNA), which accounted for 5, 50, 6, and 23% of the total HNE metabolized. The conversion of GS-HNE to GS-DHN was inhibited by tolrestat, indicating that it is catalyzed by aldose reductase (AR). The AR was also found to be an efficient catalyst for the reduction of the core aldehyde - 1-palmitoyl-2- (5-oxovaleroyl)-sn-glycero-3-phosphorylcholine, which is generated in minimally modified low-density lipoprotein, and activates the endothelium to bind monocytes. As determined by electrospray mass spectrometry, reduction of POVPC (m/z=594) by AR led to the formation of 1-palmitoyl-2- (5)-hydrovaleryl-sn-glycero-3-phosphorylcholine (PHVPC; m/z=596). These observations suggest that due to its ability to catalyze the reduction of lipid-derived aldehydes AR may be involved in preventing inflammation and diminishing oxidative stress during the early phases of atherogenesis.

Aldehyde Reductase↗

PubMed2001

Binding of pyridine nucleotide coenzymes to the beta-subunit of the voltage-sensitive K+ channel.

The beta-subunit of the voltage-sensitive K(+) (K(v)) channels belongs to the aldo-keto reductase superfamily, and the crystal structure of K(v)beta2 shows NADP bound in its active site. Here we report that K(v)beta2 displays a high affinity for NADPH (K(d) = 0.1 micrometer) and NADP(+) (K(d) = 0.3 micrometer), as determined by fluorometric titrations of the recombinant protein. The K(v)beta2 also bound NAD(H) but with 10-fold lower affinity. The site-directed mutants R264E and N333W did not bind NADPH, whereas, the K(d)(NADPH) of Q214R was 10-fold greater than the wild-type protein. The K(d)(NADPH) was unaffected by the R189M, W243Y, W243A, or Y255F mutation. The tetrameric structure of the wild-type protein was retained by the R264E mutant, indicating that NADPH binding is not a prerequisite for multimer formation. A C248S mutation caused a 5-fold decrease in K(d)(NADPH), shifted the pK(a) of K(d)(NADPH) from 6.9 to 7.4, and decreased the ionic strength dependence of NADPH binding. These results indicate that Arg-264 and Asn-333 are critical for coenzyme binding, which is regulated in part by Cys-248. The binding of both NADP(H) and NAD(H) to the protein suggests that several types of K(v)beta2-nucleotide complexes may be formed in vivo.

Amino Acid Sequence↗

PubMed2001

Identification of biochemical pathways for the metabolism of oxidized low-density lipoprotein derived aldehyde-4-hydroxy trans-2-nonenal in vascular smooth muscle cells.

Oxidation of low-density lipoproteins (LDL) generates high concentrations of unsaturated aldehydes, such as 4-hydroxy trans-2-nonenal (HNE). These aldehydes are mitogenic to vascular smooth muscle cells and sustain a vascular inflammation. Nevertheless, the processes that mediate and regulate the vascular metabolism of these aldehydes have not been examined. In this communication, we report the identification of the major metabolic pathways and products of [(3)H]-HNE in rat aortic smooth muscle cells in culture. High-performance liquid chromatography separation of the radioactivity recovered from these cells revealed that a large (60-65%) proportion of the metabolism was linked to glutathione (GSH). Electrospray mass spectrometry showed that glutathionyl-1,4 dihydroxynonene (GS-DHN) was the major metabolite of HNE in these cells. The formation of GS-DHN appears to be due aldose reductase (AR)-catalyzed reduction of glutathionyl 4-hydroxynonanal (GS-HNE), since inhibitors of AR (tolrestat or sorbinil) prevented GS-DHN formation, and increased the fraction of the glutathione conjugate remaining as GS-HNE. Gas chromatography-chemical ionization mass spectroscopy of the metabolites identified a subsidiary route of HNE metabolism leading to the formation of 4-hydroxynonanoic acid (HNA). Oxidation to HNA accounted for 25-30% of HNE metabolism. The formation of HNA was inhibited by cyanamide, indicating that the acid is derived from an aldehyde dehydrogenase (ALDH)-catalyzed pathway. The overall rate of HNE metabolism was insensitive to inhibition of AR or ALDH, although inhibition of HNA formation by cyanamide led to a corresponding increase in the fraction of HNE metabolized by the GSH-linked pathway, indicating that ALDH-catalyzed oxidation competes with glutathione conjugation. These metabolic pathways may be the key regulators of the vascular effects of HNE and oxidized LDL.

Aldehyde Reductase↗

PubMed2001

Role of tensile stress and strain in the induction of cell death in experimental vein grafts.

Tensile stress and strain are known to induce vascular cell proliferation, a process that is physiologically counterbalanced by cell death. Here we investigate whether tensile stress and strain regulate vascular-cell death by using an end-to-end anastomosed rat vein graft model. In such a model, the circumferential tensile stress in the graft wall was increased by approximately 140 times immediately after surgery compared with that in the venous wall. This change was associated with an increase in the percentage of TUNEL-positive cells at 1, 6, 24, 120, 240, and 720h with two distinct peaks at 1 and 24h (10.1+/-3.5 and 14.4+/-3.2%, respectively) compared with that in control jugular veins (0.4+/-0.5 and 0.5+/-0.5% at 1 and 24h, respectively). When tensile stress and strain in the vein graft wall were reduced by using a biomechanical engineering approach, the rate of cell death was reduced significantly (3.6+/-1.1 and 1.6+/-0.5% at 1 and 24h, respectively). Furthermore, DEVD-CHO, a tetrapeptide aldehyde that inhibits the activity of caspase 3, significantly suppressed this event. These results suggest that a step increase in tensile stress and strain in experimental vein grafts induces rapid cell death, which is possibly mediated by cell death signaling mechanisms.

Anastomosis, Surgical↗

PubMed2001

Role of blood shear stress in the regulation of vascular smooth muscle cell migration.

Smooth muscle cell (SMC) migration from the media to the intima of blood vessels contributes to neointimal formation and atherogenesis. Here, we demonstrate how blood shear stress regulates vascular SMC migration in the encapsulating tissue of a micro-cylinder implanted in the center of the rat vena cava with the micro-cylinder perpendicular to blood flow. In this model, the micro-cylinder was exposed to a laminar flow with a known shear stress field in the leading region and a vortex flow in the trailing region. After surgery, the micro-cylinder was encapsulated by a thrombus-like tissue within one day, followed by SMC migration from the vena cava to the encapsulating tissue from day 3 to 20. SMC migration was time-dependent with a peak migration speed at day 5. At each given time (excluding day 1), blood shear stress exerts an inhibitory effect on SMC migration with significantly suppressed SMC migration in the laminar flow region than in the stagnation, separation, and vortex flow regions. SMCs were relatively parallel to the shear stress direction in high shear stress regions, whereas perpendicular to the shear stress direction in low shear stress regions. These results suggest that blood shear stress plays a role in regulating SMC migration and orientation in this model.

Animals↗

PubMed2001

Growth and arginine metabolism of the wine lactic acid bacteria Lactobacillus buchneri and Oenococcus oeni at different pH values and arginine concentrations.

During malolactic fermentation (MLF) in grape must and wine, heterofermentative lactic acid bacteria may degrade arginine, leading to the formation of ammonia and citrulline, among other substances. This is of concern because ammonia increases the pH and thus the risk of growth by spoilage bacteria, and citrulline is a precursor to the formation of carcinogenic ethyl carbamate (EC). Arginine metabolism and growth of Lactobacillus buchneri CUC-3 and Oenococcus oeni strains MCW and Lo111 in wine were investigated. In contrast to L. buchneri CUC-3, both oenococci required a higher minimum pH for arginine degradation, and arginine utilization was delayed relative to the degradation of malic acid, the main aim of MLF. This allows the control of pH increase and citrulline formation from arginine metabolism by carrying out MLF with pure oenococcal cultures and inhibiting cell metabolism after malic acid depletion. MLF by arginine-degrading lactobacilli should be discouraged because arginine degradation may lead to the enhanced formation of acids from sugar degradation. A linear relationship was found between arginine degradation and citrulline excretion rates. From this data, strain-specific arginine-to-citrulline conversion ratios were calculated that ranged between 2.2 and 3.9% (wt/wt), and these ratios can be used to estimate the contribution of citrulline to the EC precursor pool from a given amount of initial arginine. Increasing arginine concentrations led to higher rates of growth of L. buchneri CUC-3 but did not increase the growth yield of either oenococcus. These results suggest the use of non-arginine-degrading oenococci for inducing MLF.

Arginine↗

PubMed2000

Acetaldehyde metabolism by wine lactic acid bacteria.

Acetaldehyde is a volatile flavor compound present in many fermented foods and is important in the production of red and white wines. Nine strains of the genera Lactobacillus and Oenococcus were able to metabolize acetaldehyde in a resting cell system, whereas two Pediococcus strains were not. Acetic acid and ethanol were produced from its degradation. A Lactobacillus and an Oenococcus were able to degrade SO(2)-bound acetaldehyde, as well. A coincubation of resting cells of Saccharomyces bayanus Première Cuvée and Oenococcus oeni Lo111 showed that strain Lo111 metabolized acetaldehyde produced by the yeast. The ability of malolactic bacteria to degrade free and SO(2)-bound acetaldehyde has implications for sensory and color qualities and the use of SO(2) in wine.

Acetaldehyde↗

PubMed2000

Cyclooxygenase-2 mediates the cardioprotective effects of the late phase of ischemic preconditioning in conscious rabbits.

We examined the role of cyclooxygenase-2 (COX-2) in the late phase of ischemic preconditioning (PC). A total of 176 conscious rabbits were used. Ischemic PC (six cycles of 4-min coronary occlusions/4-min reperfusions) resulted in a rapid increase in myocardial COX-2 mRNA levels (+231 +/- 64% at 1 h; RNase protection assay) followed 24 h later by an increase in COX-2 protein expression (+216 +/- 79%; Western blotting) and in the myocardial content of prostaglandin (PG)E(2) and 6-keto-PGF(1alpha) (+250 +/- 85% and +259 +/- 107%, respectively; enzyme immunoassay). Administration of two unrelated COX-2 selective inhibitors (NS-398 and celecoxib) 24 h after ischemic PC abolished the ischemic PC-induced increase in tissue levels of PGE(2) and 6-keto-PGF(1alpha). The same doses of NS-398 and celecoxib, given 24 h after ischemic PC, completely blocked the cardioprotective effects of late PC against both myocardial stunning and myocardial infarction, indicating that COX-2 activity is necessary for this phenomenon to occur. Neither NS-398 nor celecoxib lowered PGE(2) or 6-keto-PGF(1alpha) levels in the nonischemic region of preconditioned rabbits, indicating that constitutive COX-1 activity was unaffected. Taken together, these results demonstrate that, in conscious rabbits, up-regulation of COX-2 plays an essential role in the cardioprotection afforded by the late phase of ischemic PC. Therefore, this study identifies COX-2 as a cardioprotective protein. The analysis of arachidonic acid metabolites strongly points to PGE(2) and/or PGI(2) as the likely effectors of COX-2-dependent protection. The recognition that COX-2 mediates the antistunning and antiinfarct effects of late PC impels a reassessment of current views regarding this enzyme, which is generally regarded as detrimental.

6-Ketoprostaglandin F1 alpha↗

PubMed2000

Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype.

Activity-dependent change in the efficacy of transmission is a basic feature of many excitatory synapses in the central nervous system. The best understood postsynaptic modification involves a change in responsiveness of AMPAR (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor)-mediated currents following activation of NMDA (N-methyl-D-aspartate) receptors or Ca2+-permeable AMPARs. This process is thought to involve alteration in the number and phosphorylation state of postsynaptic AMPARs. Here we describe a new form of synaptic plasticity--a rapid and lasting change in the subunit composition and Ca2+ permeability of AMPARs at cerebellar stellate cell synapses following synaptic activity. AMPARs lacking the edited GluR2 subunit not only exhibit high Ca2+ permeability but also are blocked by intracellular polyamines. These properties have allowed us to follow directly the involvement of GluR2 subunits in synaptic transmission. Repetitive synaptic activation of Ca2+-permeable AMPARs causes a rapid reduction in Ca2+ permeability and a change in the amplitude of excitatory postsynaptic currents, owing to the incorporation of GluR2-containing AMPARs. Our experiments show that activity-induced Ca2+ influx through GluR2-lacking AMPARs controls the targeting of GluR2-containing AMPARs, implying the presence of a self-regulating mechanism.

Animals↗