共查询到18条相似文献,搜索用时 15 毫秒
1.
Although type A -aminobutyric acid (GABA) receptors (ligand-gated Cl– channels) have been extensively studied in the central nervous system, no information is available on this receptor in lung cells. We have examined the expression of GABAA receptor -subunit (GABRP) during the trans-differentiation between rat alveolar epithelial type II cells and type I cells. Rat alveolar type II cells, when cultured on plastic plates, gradually trans-differentiated into type-I-like cells and lost their GABRP mRNA expression. However, the GABRP mRNA was partially retained in the type II cells cultured on Matrigel. Keratinocyte growth factor (a mitogen of type II cells) increased GABRP expression. A detached collagen gel maintained the GABRP mRNA to a level close to that of the freshly isolated type II cells. An air–liquid interface culture system, mimicking in vivo conditions in the lung, significantly up-regulated the expression of GABRP mRNA and protein. mRNAs of the GABAA receptor 1-, 3-, 2-, 2-, and 3-subunits were also detected in rat type II cells. These results suggest that GABRP expression is differentially regulated by culture substrata, growth factor, detached gel, and an air-apical surface.This work was supported by NIH R01 HL-52146, R01 NIH-071628, and OCAST HR01-093, and AHA heartland affiliate 0255992Z (to L.L.). N.J. was supported by an AHA heartland affiliate pre-doctoral fellowship (0315256Z). 相似文献
2.
Jie Yu Jiacheng Zheng Jiajia Lin Linlu Jin Rui Yu Shinghung Mak Shengquan Hu Hongya Sun Xiang Wu Zaijun Zhang Mingyuen Lee Wahkeung Tsim Wei Su Wenhua Zhou Wei Cui Yifan Han Qinwen Wang 《Cellular and molecular neurobiology》2017,37(4):655-664
Oxidative stress-induced neuronal apoptosis plays an important role in many neurodegenerative disorders. In this study, we have shown that indirubin-3-oxime, a derivative of indirubin originally designed for leukemia therapy, could prevent hydrogen peroxide (H2O2)-induced apoptosis in both SH-SY5Y cells and primary cerebellar granule neurons. H2O2 exposure led to the increased activities of glycogen synthase kinase 3β (GSK3β) and extracellular signal-regulated kinase (ERK) in SH-SY5Y cells. Indirubin-3-oxime treatment significantly reversed the altered activity of both the PI3-K/Akt/GSK3β cascade and the ERK pathway induced by H2O2. In addition, both GSK3β and mitogen-activated protein kinase inhibitors significantly prevented H2O2-induced neuronal apoptosis. Moreover, specific inhibitors of the phosphoinositide 3-kinase (PI3-K) abolished the neuroprotective effects of indirubin-3-oxime against H2O2-induced neuronal apoptosis. These results strongly suggest that indirubin-3-oxime prevents H2O2-induced apoptosis via concurrent inhibiting GSK3β and the ERK pathway in SH-SY5Y cells, providing support for the use of indirubin-3-oxime to treat neurodegenerative disorders caused or exacerbated by oxidative stress. 相似文献
3.
Maria Rosaria Domenici Valentina Chiodi Mirko Averna Monica Armida Antonella Pèzzola Rita Pepponi Antonella Ferrante Michael Bader Kjell Fuxe Patrizia Popoli 《Purinergic signalling》2018,14(3):235-243
The A2A adenosine receptor (A2AR) is widely distributed on different cellular types in the brain, where it exerts a broad spectrum of pathophysiological functions, and for which a role in different neurodegenerative diseases has been hypothesized or demonstrated. To investigate the role of neuronal A2ARs in neurodegeneration, we evaluated in vitro and in vivo the effect of the neurotoxin 3-nitropropionic acid (3-NP) in a transgenic rat strain overexpressing A2ARs under the control of the neural-specific enolase promoter (NSEA2A rats). We recorded extracellular field potentials (FP) in corticostriatal slice and found that the synaptotoxic effect of 3-NP was significantly reduced in NSEA2A rats compared with wild-type animals (WT). In addition, after exposing corticostriatal slices to 3-NP 10 mM for 2 h, we found that striatal cell viability was significantly higher in NSEA2A rats compared to control rats. These in vitro results were confirmed by in vivo experiments: daily treatment of female rats with 3-NP 10 mg/kg for 8 days induced a selective bilateral lesion in the striatum, which was significantly reduced in NSEA2A compared to WT rats. These results demonstrate that the overexpression of the A2AR selectively at the neuronal level reduced 3-NP-induced neurodegeneration, and suggest an important function of the neuronal A2AR in the modulation of neurodegeneration. 相似文献
4.
Jiangang Tian Liufang Gu Andrew Adams Xueliang Wang Ruizhe Huang 《Molecular biotechnology》2018,60(8):533-538
To determine the protective effects of Pellino-1 against H2O2-induced apoptosis in periodontal ligament stem cells (PDLSC). We demonstrated that H2O2 decreases PDLSC viability by 40 and 50% with the concentrations of 400 and 500 μM, respectively, with an observed downregulation of Pellino-1 mRNA and protein; we further concluded that overexpression of Pellino-1 significantly lowers 8-hydroxy-2′-deoxyguanosine levels by 10% and upregulates superoxide dismutase 1, glutathione peroxidase levels, and catalase mRNA levels by 200, 40, and 250%, respectively. More importantly, we found that overexpression of Pellino-1 inhibited H2O2-induced cellular apoptosis through the activation of the NF-κB signaling pathway. Pellino-1 may be critically important for cell survival in the presence of oxidative elements; activation of the NF-κB signaling cascade was required for the overexpression of Pellino-1 to protect the cells from H2O2-induced apoptosis. 相似文献
5.
Verónica Vidal Susana García-Cerro Paula Martínez Andrea Corrales Sara Lantigua Rebeca Vidal Noemí Rueda Laurence Ozmen Maria-Clemencia Hernández Carmen Martínez-Cué 《Molecular neurobiology》2018,55(6):4745-4762
Trisomy 21 or Down syndrome (DS) is the most common cause of intellectual disability of a genetic origin. The Ts65Dn (TS) mouse, which is the most commonly used and best-characterized mouse model of DS, displays many of the cognitive, neuromorphological, and biochemical anomalies that are found in the human condition. One of the mechanisms that have been proposed to be responsible for the cognitive deficits in this mouse model is impaired GABA-mediated inhibition. Because of the well-known modulatory role of GABAA α5 subunit-containing receptors in cognitive processes, these receptors are considered to be potential targets for improving the intellectual disability in DS. The chronic administration of GABAA α5-negative allosteric modulators has been shown to be procognitive without anxiogenic or proconvulsant side effects. In the present study, we use a genetic approach to evaluate the contribution of GABAA α5 subunit-containing receptors to the cognitive, electrophysiological, and neuromorphological deficits in TS mice. We show that reducing the expression of GABAA α5 receptors by deleting one or two copies of the Gabra5 gene in TS mice partially ameliorated the cognitive impairments, improved long-term potentiation, enhanced neural differentiation and maturation, and normalized the density of the GABAergic synapse markers. Reducing the gene dosage of Gabra5 in TS mice did not induce motor alterations and anxiety or affect the viability of the mice. Our results provide further evidence of the role of GABAA α5 receptor-mediated inhibition in cognitive impairment in the TS mouse model of DS. 相似文献
6.
N. N. Razoumnaya 《Neurophysiology》2011,43(3):233-235
In experiments on rat brain slices using extracellular recording, we studied the effects of an agonist of β2 adrenoreceptors, metaproterenol (MPT), on reactions of pyramidal neurons of the hippocampal CA1 area induced by activation of GABAB receptors. Isolated application of an agonist of GABAB receptors, baclofen (10 μM), resulted in intense inhibition (by 50% or more during the 1st min of action) of orthodromic
field discharges (OFDs) in the pyramidal layer of the above-mentioned area of the hippocampus; the discharges were evoked
by electrical stimulation of Schaffer collaterals. On the 3rd to 4th min, OFDs were suppressed nearly completely. After washing
out from baclofen, the parameters of the evoked responses never completely restored to the initial level. In all cases, simultaneous
application of 150 μM MPT and 10 μM baclofen prevented full manifestation of the inhibitory effect of the latter agent on
OFDs of pyramidal neurons. The amplitude of evoked responses decreased, but the relative intensity of inhibition under these
conditions during 2-min-long application was significantly lower than that upon isolated action of baclofen. The recovery
of the amplitude of evoked responses in the course of washing out under conditions of parallel action of MPT was more rapid
and, in some cases, complete. Therefore, our experiments showed that GABAB-ergic inhibitory transmission in the rat hippocampal CA1 area in vitro can be suppressed significantly by the β2 adrenoreceptor agonist. 相似文献
7.
Severine Chaumont Caroline André David Perrais Eric Boué-Grabot Antoine Taly Maurice Garret 《The Journal of biological chemistry》2013,288(39):28254-28265
GABA-gated chloride channels (GABAARs) trafficking is involved in the regulation of fast inhibitory transmission. Here, we took advantage of a γ2(R43Q) subunit mutation linked to epilepsy in humans that considerably reduces the number of GABAARs on the cell surface to better understand the trafficking of GABAARs. Using recombinant expression in cultured rat hippocampal neurons and COS-7 cells, we showed that receptors containing γ2(R43Q) were addressed to the cell membrane but underwent clathrin-mediated dynamin-dependent endocytosis. The γ2(R43Q)-dependent endocytosis was reduced by GABAAR antagonists. These data, in addition to a new homology model, suggested that a conformational change in the extracellular domain of γ2(R43Q)-containing GABAARs increased their internalization. This led us to show that endogenous and recombinant wild-type GABAAR endocytosis in both cultured neurons and COS-7 cells can be amplified by their agonists. These findings revealed not only a direct relationship between endocytosis of GABAARs and a genetic neurological disorder but also that trafficking of these receptors can be modulated by their agonist. 相似文献
8.
Qingming Wang Huifang Sun Weilin Sha Juan Chen Liuyue Gu Dong Wang Xinhui Tang 《Biometals》2017,30(3):441-447
A novel S2O3 2? luminescent sensor (Cu2+-p-CPIP) was developed and the presence of S2O3 2? caused an obvious fluorescence enhancement at 420 nm upon excitation at 330 nm, which could be distinguished with the naked eye under a UV lamp. Remarkably, the compound exhibited excellent selective and sensitive response to S2O3 2? over other common anions with a micromolar limit of detection (0.442 μM) in DMSO/H2O (v/v, 1:1) buffer. The absorbance intensity and the color of Cu2+-p -CPIP solution changed gradually with the increase of S2O3 2? concentration. The proposed method was applied to the determination of S2O3 2? in milk samples and the recoveries were 97.5–105%. The preparation of Cu2+-p -CPIP exhibited the quick, simple and facile advantages. The results showed that Cu2+-p -CPIP can be a good candidate for simple, rapid and sensitive colorimetric detection of S2O3 2? in aqueous solution. 相似文献
9.
Growing concentrations of N2O within the atmosphere have been accompanied by decreasing δ15N values, provoking the hypothesis of a global decline in the rate of N2O reduction relative to its production in soil. We estimate that the ratio of N2O produced to N2O reduced within the soil profile has declined by about 10–25% relative to its pre-industrial value. To a smaller extent,
a reduction in the uptake of atmospheric N2O at the soil surface relative to its emission could also have contributed to the reported isotopic signal. This calls for
a greater consideration of the process of N2O reduction in soil and its role in the global turnover of N2O. 相似文献
10.
Chao-Yan Ou Yi-Ni Luo Sheng-Nan He Xiang-Fa Deng Hai-Lan Luo Zong-Xiang Yuan Hao-Yang Meng Yu-Huan Mo Shao-Jun Li Yue-Ming Jiang 《Biological trace element research》2017,176(1):143-153
Excessive intake of manganese (Mn) may cause neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has been used successfully in the treatment of Mn-induced neurotoxicity. The γ-aminobutyric acid (GABA) is related with learning and memory abilities. However, the mechanism of PAS-Na on improving Mn-induced behavioral deficits is unclear. The current study was aimed to investigate the effects of PAS-Na on Mn-induced behavioral deficits and the involvement of ultrastructural alterations and γ-aminobutyric acid (GABA) metabolism in the basal ganglia of rats. Sprague-Dawley rats received daily intraperitoneally injections of 15 mg/kg MnCl2.4H2O, 5d/week for 4 weeks, followed by a daily back subcutaneously (sc.) dose of PAS-Na (100 and 200 mg/kg), 5 days/week for another 3 or 6 weeks. Mn exposure for 4 weeks and then ceased Mn exposure for 3 or 6 weeks impaired spatial learning and memory abilities, and these effects were long-lasting. Moreover, Mn exposure caused ultrastructural alterations in the basal ganglia expressed as swollen neuronal with increasing the electron density in the protrusions structure and fuzzed the interval of neuropil, together with swollen, focal hyperplasia, and hypertrophy of astrocytes. Additionally, the results also indicated that Mn exposure increased Glu/GABA values as by feedback loops controlling GAT-1, GABAA mRNA and GABAA protein expression through decreasing GABA transporter 1(GAT-1) and GABA A receptor (GABAA) mRNA expression, and increasing GABAA protein expression in the basal ganglia. But Mn exposure had no effects on GAT-1 protein expression. PAS-Na treatment for 3 or 6 weeks effectively restored the above-mentioned adverse effects induced by Mn. In conclusion, these findings suggest the involvement of GABA metabolism and ultrastructural alterations of basal ganglia in PAS-Na’s protective effects on the spatial learning and memory abilities. 相似文献
11.
Morozevich GE Kozlova NI Cheglakov IB Ushakova NA Preobrazhenskaya ME Berman AE 《Biochemistry. Biokhimii?a》2008,73(7):791-796
Expression of alpha5beta1 integrin in the drug-resistant MCF-7/ADR breast carcinoma cells was inhibited by treatment of these cells with alpha5-specific siRNA. The decrease of alpha5beta1 expression resulted in a sharp decrease of expression of MMP-2 collagenase and inhibition of invasion activity of these cells in vitro. Similar decrease of invasion was also observed during inhibition of MMP-2 expression by treatment of these cells with MMP-2-specific siRNA. Inhibition of alpha5beta1 expression was also accompanied by significant decrease in cell content of active (phosphorylated) forms of signal protein kinases Akt and Erk1/2. Inhibition of activity of these kinases by treatment of cells with PI-3K/Akt-specific inhibitor LY294002 or Erk-specific inhibitor PD98059 resulted in inhibition of MMP-2 expression and the decrease of invasion in vitro. These data suggest that alpha5beta1 controls invasion ability of these cells by regulating expression of MMP-2, which involves PI-3K and Erk1/2 protein kinase signaling. 相似文献
12.
The fruit of the ‘Dangshansuli’ pear has a greenish yellow skin, whereas its mutant, the ‘Xiusu’ pear, has a russet skin, which represents a genetic variation. It has been demonstrated that the formation of russet fruit in the ‘Xiusu’ pear is related to lignin accumulation in skin exocarp cells. In this study, we localized hydrogen peroxide (H2O2) to the cell wall using transmission electron microscopy (TEM) and quantified the concentrations of H2O2 and polyamines. In addition, the expression levels of genes involved in polyamine biosynthesis were measured in the exocarps of samples of young fruits of ‘Dangshansuli’, ‘Xiusu’, ‘Xiusu’ treated with methylglyoxal bis(guanylhydrazone), and ‘Xiusu’ treated with ethephon. The results obtained could explain the mechanism by which H2O2 participates in polyamine metabolism in the lignification of exocarp cells in the russet fruit mutant. The TEM results showed that free H2O2 is present near the cell wall, where lignin is primarily synthesized, and the H2O2 concentration was highly positively correlated with the lignin concentration. Although H2O2 related to lignification showed no significant correlation with the putrescine or spermine concentration, it was highly positively correlated with the spermidine (Spd) concentration. Additionally, the Spd concentration was significantly positively correlated with altered expression of the polyamine oxidase gene (PbPAO). Taken together, these results have demonstrated that H2O2 involved in lignification originates from the oxidation of Spd by the enzyme PAO, with high expression of the PbPAO gene, which suggests that H2O2 from polyamine metabolism affects lignification in the exocarp of the russet mutant pear. 相似文献
13.
Guang-zhe Li Fang Liu Cui Xu Jing-yang Li Yan-ji Xu 《Biological trace element research》2018,184(2):442-449
Amyloid beta (Aβ) is the main component of the amyloid plaques that accumulate in the brains of Alzheimer patients. The present study was conducted to investigate whether the combined treatment with selenium (Se) and zinc (Zn) offers more beneficial effects than that provided by either of them alone in reversing Aβ25–35-induced neurotoxicity in PC12 cells. Cells were pretreated with 0.1 μmol/L of Se and Zn for 4 h, after treated with 10 mmol/L Aβ25–35 for 24 h. Cells were divided into control and five treated groups, and received either 10 mmol/L Aβ25–35,10 mmol/L Aβ25–35 + 0.1 μmol/L Se, 10 mmol/L Aβ25–35 + 0.1 μmol/L Zn, 10 mmol/LAβ25–35 + 0.1 μmol/L Se + 0.1 μmol/L Zn, or 0.1 μmol/L Se + 0.1 μmol/L Zn. The result showed that cell viability was decreased in MTT metabolic rate; LDH release and MDA, H2O2, and NO levels were increased and the GSK-3β and phosphorylated tau protein level were increased in Aβ25–35-treated group (P < 0.05 or P < 0.01), which whole changes were attenuated by Se and Zn and Se combined Zn. In order to evaluate whether the Se and Zn have an effect on processing pathway of amyloid precursor protein (APP), we examined the activity of γ-secretase in primary cultured cortical neuron cells. ELISA analysis showed that Se and Zn could inhibit the activity of γ-secretase. Then we also investigated the effect of Se and Zn on the Aβ1–40 concentration and APP-N-terminal fragment expression from APP695 stably transfected Chinese hamster ovary (CHO) cells. APP695 stably transfected CHO cells were treated with 0.1 μmol/L Se and Zn; cells were divided into control and four treated groups, which received either 0.5 M DAPT, 0.1 μmol/L Se, 0.1 μmol/L Zn, or 0.1 μmol/L Se + 0.1 μmol/L Zn. Se and Zn could decrease Aβ1–40 production and increase the APP-N-terminal fragment protein expression. These experiments indicate that Se and Zn have a protective effect on AD pathology that a possible mechanism is inhibiting the activity of γ-secretase to decreasing Aβ1–40 production further influencing the APP processing. Altogether, our findings may provide a novel therapeutic target to treat AD sufferers. 相似文献
14.
15.
Chin-Hsuan Hsieh Ya-Jan Hsu Chien-Chung Chang Hsin-Chun Liu Kun-Lung Chuang Cheng-Keng Chuang See-Tong Pang Kenichiro Hasumi Soldano Ferrone Shuen-Kuei Liao 《Cancer immunology, immunotherapy : CII》2009,58(3):395-408
In renal cell carcinoma (RCC), HLA class I downregulation has been found in about 40% of the lesions examined. Since only
scanty information is available about the molecular basis of these defects, we have investigated the mechanism(s) underlying
HLA class I antigen downregulation or loss in six RCC cell lines. Five of them express HLA class I antigens although at various
levels; on the other hand, HLA class I antigens are not detectable on the remaining cell line, the RCC52 cell line, belonging
to a sarcomatoid subtype, even following incubation with IFN-γ. β2-microglobulin (β2
m) was not detected in RCC52 cells. Surprisingly, RCC52 cells harbor two mutations in the β
2
m genes in exon 1: a single G deletion (delG) in codon 6, which introduces a premature stop at codon 7, and a CT dinucleotide
deletion (delCT), which leads to a premature stop at codon 55. Analysis of eight clonal sublines isolated from the RCC52 cell
line showed that the two β
2
m gene mutations are carried separately by RCC52 cell subpopulations. The delG/delCT double mutations were detected in two
sublines with a fibroblast-like morphology, while the delCT mutation was detected in the remaining six sublines with an epithelial
cell morphology. Furthermore, loss of heterozygosity (LOH) of the β
2
m gene at STR D15S-209 was found only in the epithelioid subpopulation, indicating loss of one copy of chromosome 15. Immunostaining
results of the tumor lesion from which the cell line RCC52 was originated were consistent with the phenotyping/molecular findings
of the cultured cells. This is the first example of the coexistence of distinct β
2
m defects in two different tumor subpopulations of a RCC, where loss of one copy of chromosome 15 occurs in one of the subpopulations
with total HLA class I antigen loss.
Chin-Hsuan Hsieh, Ya-Jan Hsu and Cheng-Keng Chuang contributed equally to the work. 相似文献
16.
Huirong Mao Yuanmei Guo Guangcheng Yang Bin Yang Jun Ren Sanfeng Liu Huashui Ai Junwu Ma Bertram Brenig Lusheng Huang 《BMC genetics》2008,9(1):63
Background
Limb bone lengths and bone mineral density (BMD) have been used to assess the bone growth and the risk of bone fractures in pigs, respectively. It has been suggested that limb bone lengths and BMD are under genetic control. However, the knowledge about the genetic basis of the limb bone lengths and mineralisatinon is limited in pigs. The aim of this study was to identify quantitative trait loci (QTL) affecting limb bone lengths and BMD of the distal femur in a White Duroc × Erhualian resource population.Results
Limb bone lengths and femoral bone mineral density (fBMD) were measured in a total of 1021 and 116 F2 animals, respectively. There were strong positive correlations among the lengths of limb bones and medium positive correlations between the lengths of limb bones and fBMD. A whole-genome scan involving 183 microsatellite markers across the pig genome revealed 35 QTL for the limb bone lengths and 2 for femoral BMD. The most significant QTL for the lengths of five limb bones were mapped on two chromosomes affecting all 5 limb bones traits. One was detected around 57 cM on pig chromosome (SSC) 7 with the largest F-value of more than 26 and 95% confidence intervals of less than 5 cM, providing a crucial start point to identify the causal genes for these traits. The Erhualian alleles were associated with longer limb bones. The other was located on SSCX with a peak at 50–53 cM, whereas alleles from the White Duroc breed increased the bone length. Many QTL identified are homologous to the human genomic regions containing QTL for bone-related traits and a list of interesting candidate genes.Conclusion
This study detected the QTL for the lengths of scapula, ulna, humerus and tibia and fBMD in the pig for the first time. Moreover, several new QTL for the pig femoral length were found. As correlated traits, QTL for the lengths of five limb bones were mainly located in the same genomic regions. The most promising QTL for the lengths of five limb bones on SSC7 merits further investigation.17.
Virginiae butanolide (VB) is a member of the gamma-butyrolactone autoregulators and triggers the production of streptogramin antibiotics virginiamycin M1 and S in Streptomyces virginiae. A VB biosynthetic gene (barS2) was localized in a 10-kb regulatory island which controls the virginiamycin biosynthesis/resistance of S. virginiae, and analyzed by gene disruption/complementation. The barS2 gene is flanked by barS1, another VB biosynthetic gene catalyzing stereospecific reduction of an A-factor-type precursor into a VB-type compound, and barX encoding a pleiotropic regulator for virginiamycin biosynthesis. The deduced product of barS2 possessed moderate similarity to a putative dehydrogenase of Streptomyces venezuelae, encoded by jadW2 located in similar gene arrangement to that in the regulatory island of S. virginiae. A barS2-disruptant (strain IC152), created by means of homologous recombination, showed no differences in growth in liquid medium or morphology on solid medium compared to a wild-type strain, suggesting that BarS2 does not play any role in primary metabolism or morphological differentiation of S. virginiae. In contrast, no initiation of virginiamycin production or VB production was detected with the strain IC152 until 18 h of cultivation, at which time full production of virginiamycin occurs in the wild-type strain. The delayed virginiamycin production of the strain IC152 was fully restored to the level of the wild-type strain either by the exogenous addition of VB or by complementation of the intact barS2 gene, indicating that the lack of VB production at the initiation phase of virginiamycin production is the sole reason for the defect of virginiamycin production, and the barS2 gene is of primary importance for VB biosynthesis in S. virginiae. 相似文献
18.
Jennifer M Kress-Bennett Garth D Ehrlich Ashley Bruno J Christopher Post Fen Z Hu Thomas F Scott 《BMC neurology》2011,11(1):155