Controlled ovarian hyperstimulation alters mice placental function / 解放军医学杂志

Objective To observe and assess the effect of controlled ovarian hyperstimulation (COH) on fetal weight and placental function of mouse model. Methods In vitro fertilized (IVF) blastocysts were transferred to non-stimulated pseudopregnant mice (NSP group, n=6) and superovulated pseudopregnantt mice (SOP group, n=6). At 18.5 d of embryonic age (E18.5 d), the fetal weight and placental weight were examined. The areas of labyrinth layer and junction layer of placenta were measured using microscopic image software. The apoptosis in the placenta was detected by TUNEL. The levels of glutathion (GSH) and malonaldehyde (MDA) in placenta were detected separately by spectrophotometry and barbiturate method. The expression levels of amino acid transporter Snat1, Snat2, Snat4, Lat1, Lat2, Cd98, and Taut mRNA in placenta were detected by qRT-PCR. The SNAT2 protein levels in microvillous membrane (MVM) of placenta were detected by Western blotting. Results At E18.5d, compared with the mice in SOP group to those in NSP group, the mean weights of fetal and placenta were significantly lower [(1.37±0.13) g vs. (1.75±0.13) g; (0.14±0.02) g vs. (0.17±0.01) g, P<0.001)]. The apoptosis rates increased in both labyrinth layer and junction layer of placenta [(7.57±1.23) % vs. (4.62±0.91) %, P<0.001; (5.28±0.99) % vs. (3.27±0.69) %, P=0.002]. The GSH level in placenta decreased obviously [(5.21±1.55) μmol/g prot vs. (8.45±1.60) μmol/g prot, P=0.005], while the concentration of MDA increased markedly [(1.35±0.52) nmol/g prot vs. (0.56±0.19) nmol/g prot, P=0.005]. The levels of Snat1, Snat2, Lat2 and Tau mRNA in the placenta were down regulated (0.77±0.13, 0.65±0.18, 0.69±0.18, 0.73±0.07, P<0.001), and the SANT2 protein levels in placental MVM were decreased significantly [(0.32±0.01) vs. (0.65±0.15), P<0.001]. Conclusion Controlled ovarian hyperstimulation may alter placental function, and induced placental oxidative stress might be a critical factor of abnormal placental function.

Role of μ-δ heterodimer in down-regulation of expression of excitatory amino acid transporter 3 in hippocampi caused by reinstatement of morphine-induced conditioned place preference in rats / 中华麻醉学杂志

Objective To evaluate the role of μ-δ heterodimer in down-regulation of the expression of excitatory amino acid transporter 3 (EAAT3) in hippocampi caused by reinstatement of morphine-induced conditioned place preference (CPP) in rats.Methods Thirty-two healthy clean-grade male Sprague-Dawley rats,weighing 200-240 g,were assigned into 4 groups (n =8 each) using a random number table method:control group (group C),extinction group (group E),reinstatement group (group R) and reinstatement plus interference plasmid group (group RI).The model of morphine-induced CPP was established,and extinction of CPP was gradually induced by stopping administration.A small dose of morphine 5 mg/kg was intraperitoneally injected again to induce CPP reinstatement,and dwell time around the medicine box was recorded.μ-δ heterodimer interference plasmid 5 μl was injected into the lateral cerebral ventricle after successful establishment of CPP model in group RI.The content of glutamate (Glu) in hippocampi was measured using high-performance liquid chromatography.The EAAT3 expression in hippocampal CA1 and CA3 regions was detected using Western blot.Results Compared with group C,no significant change was found in the dwell time around the medicine box or content of Glu in hippocampi (P＞0.05),and the expression of EAAT3 in hippocampal CA1 and CA3 regions was significantly up-regulated in group E,and the dwell time around the medicine box was significantly prolonged,the content of Glu in hippocampi was increased (P＜0.05),and no significant change was found in the expression of EAAT3 in hippocampal CA1 and CA3 regions in group R (P＞0.05).Compared with group E,the dwell time around the medicine box was significantly prolonged,the content of Glu in hippocampi was increased,and the expression of EAAT3 in hippocampal CA1 and CA3 regions was down-regulated in group R (P＜0.05).Compared with group R,the dwell time around the medicine box was significantly shortened,the content of Glu in hippocampi was decreased,and the expression of EAAT3 in hippocampal CA 1 and CA3 regions was upregulated in group RI (P＜0.05).Conclusion μ-δ heterodimer is involved in down-regulation of EAAT3 expression in the hippocampus caused by reinstatement of morphine-induced CPP in rats.

Role of EAAT2 in cannabinoid receptor 2 activation-induced attenuation of microglial injury caused by glutamate / 中华麻醉学杂志

Objective To evaluate the role of excitatory amino acid transporter 2 ( EAAT2) in can-nabinoid receptor 2 ( CB2 receptor) activation-induced attenuation of microglial injury caused by glutamate. Methods N9 microglial cells were divided into 4 groups ( n=26 each) using a random number table meth-od: control group ( group Con) , glutamate group ( group Glu) , CB2 receptor agonist AM1241 plus gluta-mate group (group AM1241+Glu) and AM1241 plus EAAT inhibitor TBOA plus glutamate group (group AM1241+TBOA+Glu) . The cells were routinely cultured for 30 h in group Con. In group Glu, the cells were routinely cultured for 6 h, and then were incubated for 24 h in the culture medium containing gluta-mate 10 mmol∕L. In group AM1241+Glu, the cells were incubated for 4 h in the culture medium containing AM12412 μmol∕L, and then were routinely cultured for 2 h, and then were incubated for 24 h in the cul-ture medium containing glutamate 10 mmol∕L. In group AM1241+TBOA+Glu, the cells were incubated for 4 h in the culture medium containing AM12412 μmol∕L and TBOA 100 μmol∕L, and then were routinely cultured for 2 h, and then were incubated for 24 h in the culture medium containing glutamate 10 mmol∕L. The cell viability was measured by MTT assay, the activity of lactic dehydrogenase ( LDH) in supernatant was determined using colorimetric method, and the expression of EAAT2 was determined by Western blot. Results Compared with group Con, the cell viability was significantly decreased and LDH activity was in-creased in Glu, AM1241+Glu and AM1241+TBOA+Glu groups, and the expression of EAAT2 was signifi-cantly up-regulated in Glu and AM1241+Glu groups ( P<0. 05) . Compared with group Glu, the cell viabil-ity was significantly increased, LDH activity was decreased, and the expression of EAAT2 was up-regulated in group AM1241+Glu ( P<0. 05) , and no significant change was found in the parameters mentioned above in group AM1241+TBOA+Glu ( P>0. 05) . Compared with group AM1241+Glu, the cell viability was sig-nificantly decreased, LDH activity was increased, and the expression of EAAT2 was down-regulated in group AM1241+TBOA+Glu ( P<0. 05) . Conclusion The mechanism by which the activation of CB2 re-ceptor attenuates microglial injury caused by glutamate is related to up-regulating the expression of EAAT2.

Roles and mechanisms of connexin 43 in cerebral ischemia-reperfusion / 国际脑血管病杂志

In the central nervous system, gap junctions exist between neurons and glial cells. Among them, connexin 43 (Cx43) is one of the most abundant connexin proteins in the central nervous system,involved in the metabolic coupling of intercellular substance exchange and electrical coupling of electrical signaling. It plays an important role in regulating cell metabolism, homeostasis, and cell differentiation. After cerebral ischemia, the uncoupling of gap junctions and abnormal hemichannel activity cause a steady-state imbalance of the internal and external environment of the cells, eventually leading to brain tissue damage.Therefore, maintaining the normal function of Cx43 is essential for protecting brain tissue from neuronal damage induced by cerebral ischemia-reperfusion.

Effect of rhynchophylline on the mRNA expression of excitatory amino acid transporter 2 and NMDA receptor 2B after oxygen-glucose deprivation in cultured rat hippocampal astrocytes / 国际脑血管病杂志

Objective To investigate the effect of rhynchophylline on mRNA expression of excitatory amino acid transporter 2 (EAAT2 ) and N-methyl-D-aspartic acid receptor 2B (NR2B) after astrocyte oxygen-glucose deprivation. Methods The subcultured third generation astrocytes from the hippocampus were inoculated into 6-well plates, and they were divided into blank control group, hypoxia-ischemia group,low-dose rhynchophylline group (0. 02 mg/ml) and high-dose rhynchophylline group (0. 2 mg/ml) after the cells were attached to the wall and grew out protrusion. The total RNAs in each group were extracted.Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of EAAT2 and NR2B mRNA in astrocytes of each group. Results Compared with the blank control group, the expression levels of NR2B and EAAT2 mRNA in astrocytes of the ischemia-hypoxia group were significantly higher (all P < 0. 05 ). The expression levels of NR2B and EAAT2 mRNA in the low-dose rhynchophylline group were lower than those in ischemia-hypoxia group, but there was no significant difference. The expression levels of NR2B and EAAT2 mRNA in the high-dose rhynchophylline group were significantly lower than the ischemia-hypoxia group and the low-dose rhynchophylline group (all P < 0. 05).Conclusion The expression of EAAT2 and NR2B mRNA in astrocytes of hippocampus cultured in vitro was significantly increased after ischemia and hypoxia, and rhynchophylline intervention could significantly reduce its expression in a concentration dependent manner.

The effect of low protein on colonic mucosal barrier in pigs / El efecto de baja proteína en la barrera mucosa colónica en cerdos

Reducing nitrogen nutrients concentration in dairy food is economic for pig industry. Here, we used finishing pig as model to investigate the effect on colon mucosal barrier and nutrients absorption after reducing crude protein (CP) in dietary from 16 % to 13 %. The results showed that crypt depth, cells, claudin-1 and E-cadherin expression level will not be changed, which implied the integrity of colon mucosal structure. Furthermore, the expressions of ASCT1, EAAT3 and SGLT1 in colon were also maintained at normal levels in 13 % CP dietary. Interestingly, the CAT1 and GLUT2 expression were increased significantly after reducing CP level to 13 %, which might be attributed to the compensatory nutrients absorption. This study implied that 13 % CP was sufficient to maintain normal colon structure and will not change intestinal morphology, which provided a basis for an ideal economic protein feed formula.

La reducción de concentración de nitrógeno en los alimentos lácteos es económicamente favorable para la industria porcina. En este trabajo se utilizó el cerdo de acabado como modelo para investigar el efecto sobre la barrera de la mucosa del colon y la absorción de nutrientes después de reducir la proteína bruta (CP) en la dieta del 16 % al 13 %. Los resultados mostraron que la profundidad de la cripta, las células globulares, el nivel de expresión de Claudin-1 y E-cadherina no cambiaron, lo que implicaría la integridad de la estructura de la mucosa del colon. Además, las expresiones de ASCT1, EAAT3 y SGLT1 en el colon también se mantuvieron en niveles normales en el 13 % de la dieta de CP. Sin embargo, la expresión de CAT1 y GLUT2 incrementó significativamente después de reducir el nivel de CP a 13 %, lo que podría atribuirse a la absorción de nutrientes compensatorios. Este estudio indicó que el CP del 13 % era suficiente para mantener la estructura normal del colon y no cambiaría la morfología intestinal, lo que proporcionó una base para una fórmula económica ideal para la alimentación con proteínas.

JPH203, a selective L-type amino acid transporter 1 inhibitor, induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells

Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, potently inhibited L-leucine uptake in Saos2 cells. As expected, the intrinsic ability of JPH203 to inhibit L-leucine uptake was far more efficient than that of BCH in Saos2 cells. Likewise, JPH203 and BCH inhibited Saos2 cell growth with JPH203 being superior to BCH in this regard. Furthermore, JPH203 increased apoptosis rates and formed DNA ladder in Saos2 cells. Moreover, JPH203 activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. These results suggest that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells.

Role of system A amino acid transporter in fetal intrauterine growth restriction / 中国基层医药

Fetal intrauterine growth restriction is one of the common diseases in the perinatal period,which not only increases the child morbidity and mortality in the perinatal period,affecting the long-term development of the nervous system,and can make the risk of adult obesity,hypertension,type Ⅱ diabetes increased significantly.A number of studies suggest that the down-regulation of A amino acid transporter expression is closely associated with intrauterine growth restriction.The down-regulation of A amino acid transporter expression may be an important cause of intrauterine growth restriction.

Effects of isoflurane on expression of GFAP and EAAT2 in neonatal rats brian / 中国药学杂志

OBJECTIVE: To investigate the effects of prolonged exposure to isoflurane on the expression of glial fibrillary acidic protein (GFAP) and excitatory amino acid transporter-2 (EAAT2) in cortex of frontal lobe and hippocampus of neonatal rats. METHODS: Forty Wistar rats at postnatal day 7 were randomly divided into isoflurane group and control group according to the random number table method (n=20). Isoflurane group were exposed to 1.1% isoflurane (equivalent to 0.5 MAC for neonatal rats) for 6 h, the others were exposed to the gas mixture of 30% of the oxygen and nitrogen for 6 h in the control group. Five neonatal rats were sacrificed 12, 24 h, 3 and 7 d after exposure in each group. The brain were frozen and sliced, brain sections were double-stained with GFAP and EAAT2 markers. The fluorescence intensity of GFAP and EAAT2 double-labeled immunofluorescence was quantified in cortex of frontal lobe and hippocampus at 12, 24 h, 3 and 7 d after exposure by the Image J programme. RESULTS: Compared with the control group, the immunofluorescence intensity of GFAP in cortex of frontal lobe after exposure 12, 24 h in isoflurane group was significantly decreased(P < 0.01), whereas there was no significant difference after exposure 3, 7 d. The immunofluorescence intensity of GFAP in hippocampus after exposure 12, 24 h and 3 d in isoflurane group decreased compared with control group(P < 0.01), except 7 d after exposure. Double-labeled immunofluorescence showed lowered expression of GFAP and EAAT2 co-stained region in cortex of frontal lobe and hippocampus at 12, 24 h, 3 and 7 d after exposure in isoflurane group when compared with control group(P < 0.01). CONCLUSION: The 1.1% isoflurane prolonged exposure transiently reduces the expression of GFAP in the cortex and hippocampus, and delays the development of cytoskeleton. Whereas inhibiting the expression EAAT2 of astrocytes is prolonged, that may be one of the mechanisms for isoflurane-induced neurotoxicity.

Effect of Phenolic Alkaloids from Menispermum dauricum on EAAC1 mRNA Expression in Hippocampal Neurons of Rats with Focal Cerebral Ischemia / 医药导报

Objective To investigate the effect of phenolic alkaloids from Menispermum dauricum( PAMd)on the mRNA expression of the glutamate transporter EAAC1 in hippocampal neurons of rats subjected to focal cerebral ischemia and to elucidate its neuroprotective mechanisms. Methods A total of 42 Sprague Dawley(SD)rats were randomly divided into three groups:sham group,model control group,and PAMd(10 mg·kg-1 ,i.g)group(n = 14 each).The focal cerebral ischemia model of rat was induced by the middle cerebral artery occlusion( MCAO). The 2,3,5-triphenyltetrazolium chloride( TTC) staining was applied to measure the cerebral infarct size and the reverse transcriptase-polymerase chain reaction(RT-PCR)assay to detect EAAC1 mRNA expression in hippocampal neurons. Results After 24 h ischemia,the cerebral infarct volumes were (0.0±0.0)%,(35.3±2.9)% and(21.3±3.8)% in sham group,model control group and PAMd group,respectively(P<0.05). The relative expression levels of EAAC1 mRNA were 0.97±0.04,2.46±0.13,and 1.91±0.15 in the three groups,respectively (P<0. 05). Conclusion PAMd may protect against cerebral ischemia by up-regulating EAAC1 mRNA expression and alleviating the excitotoxicity of glutamic acid.

Current research of L-amino acid transporter 1 in tumor diagnosis and treatment / 天津医药

L-amino acid transporter 1 ( LAT1) is a member of L-amino transporter family and an important heterodi?meric amino acid transporter that belongs to subfamily of SLC7. LAT1 mainly mediates trans-membrane transportation of those neutral amino acids that had cyclobenzene or long side chains with high molecular mass such as L-Leu, L-Met and L-Phe as well as some amino acid analogues such as melphalan, L-DOPA and thyroxine in a Na+and ATP-independent diffu?sion. As LAT1 was abnormally overexpressed in various transformed cell lines, it might be related with tumor stage and prog?nosis. It is not only a biomarker that specifically expressed in some tumor cells but also plays an important role in tumor diag?nosis and therapy. Here we demonstrate the structure of LAT1 and its mechanism in transport peculiarity. We also reviewed the development of LAT1 in tumor diagnosis and treatment.

Effect of LAT1 on early placenta formation in mice / 中国实验动物学报

Objective To explore the expression and role of LAT 1 in mouse uterus on early placenta formation on day 8 of pregnancy (D8).Methods One hundred and twenty 6-8-week old SPF female Kunming mice were used in this study.Immunohistochemistry was applied to determine the localization of LAT 1 protein in the mouse uterus on D8 of preg-nancy.The ectoplacental cones (EPCs) were dissected out from D8.5 uterus, and then cultured in vitro with different con-centrations of BCH (2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, specific antagonist of LAT1) and L-leucine ( substrate of LAT1) to determine the role of LAT1 during the EPC attachment and outgrowth .Results LAT1 protein was highly expressed in secondary decidual zone and also positively expressed in the mouse uterus on D 8.As a specific antago-nist of LAT1, BCH significantly suppressed the ectoplacental cone outgrowth , whereas L-leucine showed no significant effect on it.Conclusions LAT1 is expressed in the mouse uterus during early placenta formation and promotes ectoplacen -tal cone outgrowth , suggesting that LAT1 may promote the trophoblast invasion into maternal decidual tissue , and partici-pates in the early formation of placenta .

Glutamate transporter-1 and cerebral ischemia / 国际脑血管病杂志

Glutamate is an essential excitatory neurotransmitter which regulates brain functions.An increase in extracellular glutamate could excessively activate ionotropic glutamate receptors,initiate calcium overload,and lead to cell death after cerebral ischemia.Glutamate transporter-1 (GLT-1) is one of the major glutamate transporters expressed predominantly in astrocytes.Astrocytes also express the enzyme glutamine synthetase (GS) which converts the glutamate to glutamine; the latter is then 'recycled' into neurons.Pretreatment with ceftriaxone (CEF),ischemia and intermittent hypobaric hypoxia could lead to neuroprotection by increasing the expression of GLT-1 and regulating the activity of glutamate transporter in brain.

Effect of propofol on oxidative stress-attenuated glutamate transporter EAAT4 activity

BACKGROUND: Propofol (2, 6-diisopropylphenol) has been known to have neuroprotective effects. Excitatory amino acid transporter 4 (EAAT4) is a glutamate transporter predominantly expressed in the cerebellar Purkinje cells, which is vulnerable to ischemic injury. Thus, we hypothesized that propofol reverses reduced EAAT4 activity which was induced by oxidative stress and investigated the effects of propofol on EAAT4 under oxidative stress induced by tert-butyl hydroperoside (t-BHP). METHODS: EAAT4 was expressed in Xenopus oocytes by injection of its mRNA. By using two-electrode voltage clamping, membrane currents were recorded before, during, and after application of L-aspartate (3 microM) in the presence or absence of t-BHP and propofol. RESULTS: L-aspartate induced an inward current in EAAT4 expressing oocytes. Exposure of these oocytes to t-BHP (1-20 mM) for 10 min dose-dependently decreased EAAT4 activity (1 +/- 0.01 microC for control; 0.88 +/- 0.05 microC for 1 mM; 0.83 +/- 0.03 microC for 2mM; 0.65 +/- 0.04 microC for 3 mM; 0.51 +/- 0.07 microC for 5 mM; 0.45 +/- 0.03 f microC for 10 mM and 0.24 +/- 0.06 microC for 20 mM). IC50 for t-BTH was 6.05 mM and further study was performed with 10 mM t-BTH. Propofol (3-10 microM) dose-dependently reversed this t-BHP-attenuated EAAT4 activity. CONCLUSIONS: Oxidative stress by t-BHP decreased EAAT4 activity and 3-10 microM propofol restored oxidative stress-reduced EAAT4 activity.

Berberine attenuates impairment of intestinal glutamine transport in sepsis / 肠外与肠内营养

Objective: A marked deficiency of glutamine in clinical critical illness is correlated with mortality in the intensive care unit, and intestinal glutamine transport was reported to be impaired in late sepsis. Berberine was reported to protect against the intestine injury, and improve the survival rate in sepsis. We designed this study to gain further knowledge of the intestinal glutamine transport in early and late sepsis, and to find out whether beberine pretreatment has some effect on glutamine transport in sepsis. Methods: Berberine (50 mg/kg) was given intragastrically once a day for 5 days, and sepsis was induced by cecal ligation and puncture on day 5. The small intestinal samples were collected at 0, 2, 6, 12, 24 h. Intestinal brush border membrane vesicles were prepared by Mg~(2+) aggregation-differential centrifugation techniques, and brush border glutamine transport was studied by a rapid filtration technique. Results: Under control condition, Na~+-dependent glutamine transport accounted for about 90% of the total transport. The relative contributions of ATA2, ATB~(0,+), B~0AT1 were about 12, 25, 63%, respectively. Septic rats showed an early increase and a late decrease in intestinal glutamine transport. ATA2 had an earlier increase in the early stage, while B0AT1 had no significant increase. Berberine pretreated group had a relative less increase in early phase and a less decrease in late phase compared to sepsis group. Conclusion: Rat intestinal glutamine transport showed an early increase and a late decrease in sepsis, and berberine pretreatment could attenuate the impairment of glutamine transport in sepsis. It may provide some information for sepsis treatment.

Change in the expression of excitatory amino acid transporter 3 in the spinal cord neurons in a rat model of chronic morphine-tolerance / 中华麻醉学杂志

Objective To investigate the change in the expression of excitatory amino acid transporter 3 (EAAT3) in the spinal cord neurons in a rat model of chronic morphine tolerance. Methods Forty-five male SD rats were randomly divided into 5 groups ( n = 9 each) : group I sham operation (group S); group II normal saline (group NS); group Ⅰ morphine (group M); group Ⅳ ketamine (group K) and groupV M + K. In group II - V a catheter was placed in the subarachnoid space at L_(3-5) interspace. The animals were observed for 3 days. The animals with motor or sensory paralysis of the hindlimbs were excluded. NS 40 μl,morphine 20 μg, ketamine 30μg,morphine 20μg + ketamine 30μg were injected via intrathecal catheter twice a day for 7 consecutive days. 50% paw withdrawal threshold and latency (PWT, PWL) of the hindpaw to radiant heat were measured before (T_0, baseline) , on day 1, 3, 5, 7 of (T_(1-4)) and 1 day after (T_5 ) IT drug administration. The rats were sacrificed after last pain threshold measurement. The expression of EAAT3 protein in the spinal cord was determined by Western blotting and immuno-histochemistry. Results The sensitivity of the hindpaw to noxious heat stimulation was significantly decreased during (T_(1,2)) and increased after IT administration (T_(4,5)) in group M and was significantly decreased during and after FT administration (T_(1-5)) in group M + K as compared with the baseline values at T_0 and group S and was significant lower in group M + K than in group M. The expression of EAAT3 protein in the spinal cord was significantly decreased in group M and M + K as compared with group S and was significantly lower in group M than in group M + K. Conclusion The down-regulation of the expression of EAAT3 in the spinal dorsal horn neurons is involved in the development of chronic morphine tolerance and the expression of EAAT3 is down-regulated by morphine partly through the activation of NMDA receptor.

Expression of GLT-1 in rats hippocampus of early-onset sub-clinical seizures following acute cerebral infarction / 中华神经科杂志

Objective To explore the mechanism of early-onset sub-clinical seizures following acute cerebral infarction. Methods Right middle cerebral artery occlusion (MCAO) rats models were made by threads methods. Sub-clinical seizures were detected with recording apparatus at the same time. Glial glutamate transporter-1 (GLT-1) were detected by immunohistochemical method in rats hippocampus. Results Sub-clinical seizures occurred in 27.4% rats following MCAO. The GLT-1 expressions in CA_1 and CA_3 regions were lower in sub-clinical seizure group[(344.5?35.0)?m~2 and (360.4?13.5)?m~2 respectively] than those in the controls[(447.0?22.8)?m~2 in CA_1 region and (402.3?28.5)?m~2 in CA_3 region]. But there were not significant differences of GLT-1 immunoreactivities in dentate gyrus between the two groups above. Conclusion Early-onset sub-clinical seizures occur following the acute MCAO in rats, which should be related to the decreased expression of GLT-1 in CA_1 and CA_3 of hippocampus.

Physiological, Pharmacological and Toxicological Implications of Heterodimeric Amino Acid Transporters

The heterodimeric amino acid transporter family is a subfamily of SLC7 solute transporter family which includes 14-transmembrane cationic amino acid transporters and 12-transmembrane heterodimeric amino acid transporters. The members of heterodimeric amino acid transporter family are linked via a disulfide bond to single membrane spanning glycoproteins such as 4F2hc (4F2 heavy chain) and rBAT (related to b0, +-amino acid transporter). Six members are associated with 4F2hc and one is linked to rBAT. Two additional members were identified as ones associated with unknown heavy chains. The members of heterodimeric amino acid transporter family exhibit diverse substrate selectivity and are expressed in variety of tissues. They play variety of physiological roles including epithelial transport of amino acids as well as the roles to provide cells in general with amino acids for cellular nutrition. The dysfunction or hyperfunction of the members of the heterodimeric amino acid transporter family are involved in some diseases and pathologic conditions. The genetic defects of the renal and intestinal transporters b0, +AT/BAT1 (b0, +-type amino acid transporter/b0, +-type amino acid transporter 1) and y+LAT1 (y+L-type amino acid transporter 1) result in the amino aciduria with sever clinical symptoms such as cystinuria and lysin uric protein intolerance, respectively. LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x-C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after brain ischemia. Because of broad substrate selectivity, system L transporters such as LAT1 transport amino acid-related compounds including L-Dopa and function as a drug transporter. System L also interacts with some environmental toxins with amino acid-related structure such as cysteine-conjugated methylmercury. Therefore, these transporter would be candidates for drug targets based on new therapeutic strategies.

The neutral amino acid transporter ASCT2 in intestinal brush-border membrane:molecular and functional characteristics / 肠外与肠内营养

ASCT2 is a Na+-dependent neutral amino acid transporter in brush-border membrane of intestinal epithelial cells.The activity accounts for the majority of intestinal luminal neutral amino acid absorption,such as alanine,serine,cysteine,threonine,glutamine,asparagine and so on.The study about molecular and functional characteristics of ASCT2 will help to the understanding of bowel function,and offer the potential for developing new treatments for short bowel syndrome and other bowel dysfunction conditions.