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61.
The K–Cl cotransporter (KCC) functions in maintaining chloride and volume homeostasis in a variety of cells. In the process of cloning the mouse KCC3 cDNA, we came across a cloning mutation (E289G) that rendered the cotransporter inactive in functional assays in Xenopus laevis oocytes. Through biochemical studies, we demonstrate that the mutant E289G cotransporter is glycosylation-deficient, does not move beyond the endoplasmic reticulum or the early Golgi, and thus fails to reach the plasma membrane. We establish through co-immunoprecipitation experiments that both wild-type and mutant KCC3 with KCC2 results in the formation of hetero-dimers. We further demonstrate that formation of these hetero-dimers prevents the proper trafficking of the cotransporter to the plasma membrane, resulting in a significant decrease in cotransporter function. This effect is due to interaction between the K–Cl cotransporter isoforms, as this was not observed when KCC3-E289G was co-expressed with NKCC1. Our studies also reveal that the glutamic acid residue is essential to K–Cl cotransporter function, as the corresponding mutation in KCC2 also leads to an absence of function. Interestingly, mutation of this conserved glutamic acid residue in the Na+-dependent cation-chloride cotransporters had no effect on NKCC1 function in isosmotic conditions, but diminished cotransporter activity under hypertonicity. Together, our data show that the glutamic acid residue (E289) is essential for proper trafficking and function of KCCs and that expression of a non-functional but full-length K–Cl cotransporter might results in dominant-negative effects on other K–Cl cotransporters. 相似文献
62.
63.
Sisi Guan Li Li Wen-Shu Chen Wen-Yang Jiang Yun Ding Li-Lan Zhao Yi-Fan Shi Jun Wang Qi Gui Cheng-Cheng Xu Yang Cheng Wenjuan Zhang 《Journal of cellular and molecular medicine》2021,25(20):9784-9795
Circular RNA is a newly discovered member of non-coding RNA (ncRNA) and regulates the target gene by acting as a micro-RNA sponge. It plays vital roles in various diseases. However, the functions of circular RNA in non-small cell lung cancer (NSCLC) remain still unclear. Our data showed that circ-WHSC1 was highly expressed in NSCLC cells and tissues. Both in vitro and in vivo experiments showed that circ-WHSC1 promoted NSCLC proliferation. circ-WHSC1 also promoted the migration and invasion of lung cancer cells. Through bioinformatic analysis and functional experiments, we showed that circ-WHSC1 could act as a sponge for micro-RNA-7 (miR-7) and regulate the expression of TAB2 (TGF-beta activated kinase one binding protein two). Inhibition of the circ-WHSC1/miR-7/TAB2 pathway could effectively attenuate lung cancer progression. In summary, this study confirmed the existence and oncogenic function of circ-WHSC1 in NSCLC. The research suggests that the circ-WHSC1/miR-7/TAB2 axis might be a potential target for NSCLC therapy. 相似文献
64.
Xin Lu JianFeng Liu WeiXuan Fu JiaPeng Zhou YanRu Luo XiangDong Ding Yang Liu Qin Zhang 《PloS one》2013,8(10)
Increased disease resistance through improved immune capacity would be beneficial for the welfare and productivity of farm animals. To identify genomic regions responsible for immune capacity traits in swine, a genome-wide association study was conducted. In total, 675 pigs were included. At 21 days of age, all piglets were vaccinated with modified live classical swine fever vaccine. Blood samples were sampled when the piglets were 20 and 35 days of age, respectively. Four traits, including Interferon-gamma (IFN-γ) and Interleukin 10 (IL-10) levels, the ratio of IFN-γ to IL-10 and Immunoglobulin G (IgG) blocking percentage to CSFV in serum were measured. All the samples were genotyped for 62,163 single nucleotide polymorphisms (SNP) using the Illumina porcineSNP60k BeadChip. After quality control, 46,079 SNPs were selected for association tests based on a single-locus regression model. To tackle the issue of multiple testing, 10,000 permutations were performed to determine the chromosome-wise and genome-wise significance level. In total, 32 SNPs with chromosome-wise significance level (including 4 SNPs with genome-wise significance level) were identified. These SNPs account for 3.23% to 13.81% of the total phenotypic variance individually. For the four traits, the numbers of significant SNPs range from 5 to 15, which jointly account for 37.52%, 82.94%, 26.74% and 24.16% of the total phenotypic variance of IFN-γ, IL-10, IFN-γ/IL-10, and IgG, respectively. Several significant SNPs are located within the QTL regions reported in previous studies. Furthermore, several significant SNPs fall into the regions which harbour a number of known immunity-related genes. Results herein lay a preliminary foundation for further identifying the causal mutations affecting swine immune capacity in follow-up studies. 相似文献
65.
Colin F. Greineder Ann-Marie Chacko Sergei Zaytsev Blaine J. Zern Ronald Carnemolla Elizabeth D. Hood Jingyan Han Bi-Sen Ding Charles T. Esmon Vladimir R. Muzykantov 《PloS one》2013,8(11)
The use of targeted therapeutics to replenish pathologically deficient proteins on the luminal endothelial membrane has the potential to revolutionize emergency and cardiovascular medicine. Untargeted recombinant proteins, like activated protein C (APC) and thrombomodulin (TM), have demonstrated beneficial effects in acute vascular disorders, but have failed to have a major impact on clinical care. We recently reported that TM fused with an scFv antibody fragment to platelet endothelial cell adhesion molecule-1 (PECAM-1) exerts therapeutic effects superior to untargeted TM. PECAM-1 is localized to cell-cell junctions, however, whereas the endothelial protein C receptor (EPCR), the key co-factor of TM/APC, is exposed in the apical membrane. Here we tested whether anchoring TM to the intercellular adhesion molecule (ICAM-1) favors scFv/TM collaboration with EPCR. Indeed: i) endothelial targeting scFv/TM to ICAM-1 provides ∼15-fold greater activation of protein C than its PECAM-targeted counterpart; ii) blocking EPCR reduces protein C activation by scFv/TM anchored to endothelial ICAM-1, but not PECAM-1; and iii) anti-ICAM scFv/TM fusion provides more profound anti-inflammatory effects than anti-PECAM scFv/TM in a mouse model of acute lung injury. These findings, obtained using new translational constructs, emphasize the importance of targeting protein therapeutics to the proper surface determinant, in order to optimize their microenvironment and beneficial effects. 相似文献
66.
Zizhen Yao Cindy T.J. van Velthoven Thuc Nghi Nguyen Jeff Goldy Adriana E. Sedeno-Cortes Fahimeh Baftizadeh Darren Bertagnolli Tamara Casper Megan Chiang Kirsten Crichton Song-Lin Ding Olivia Fong Emma Garren Alexandra Glandon Nathan W. Gouwens James Gray Lucas T. Graybuck Michael J. Hawrylycz Hongkui Zeng 《Cell》2021,184(12):3222-3241.e26
67.
68.
Iron–sulfur clusters are one of the most ubiquitous redox centers in biology. Ironically, iron-sulfur clusters are highly
sensitive to reactive oxygen species. Disruption of iron-sulfur clusters will not only change the activity of proteins that
host iron–sulfur clusters, the iron released from the disrupted iron–sulfur clusters will further promote the production of
deleterious hydroxyl free radicals via the Fenton reaction. Here, we report that ferritin A (FtnA), a major iron-storage protein
in Escherichia coli, is able to scavenge the iron released from the disrupted iron–sulfur clusters and alleviates the production of hydroxyl
free radicals. Furthermore, we find that the iron stored in FtnA can be retrieved by an iron chaperon IscA for the re-assembly
of the iron–sulfur cluster in a proposed scaffold IscU in the presence of the thioredoxin reductase system which emulates
normal intracellular redox potential. The results suggest that E. coli FtnA may act as an iron buffer to sequester the iron released from the disrupted iron–sulfur clusters under oxidative stress
conditions and to facilitate the re-assembly of the disrupted iron–sulfur clusters under normal physiological conditions. 相似文献
69.
Junfeng Dou Wei Qin Jing Yuan Aizhong Ding En Xie Yingying Wang 《Bioremediation Journal》2014,18(3):248-257
A pure strain of Microbacterium lacticum DJ-1 capable of anaer-obic biodegradation of ethylbenzene was isolated from soil contaminated with gasoline. Growth of the strain and biodegradation of ethylbenzene in batch cultures led to stoichiometric reduction of nitrate. M. lacticum DJ-1 could degrade 100 mg L?1 of ethylbenzene completely, with a maximum degradation rate of 15.02 ± 1.14 mg L?1 day?1. Increasing the initial concentration of ethy-lbenzene resulted in decreased degradative ability. The cell-specific growth rates on ethylbenzene conformed to the Haldane–Andrew model in the substrate level range of 10–150 mg L?1. Kinetic parameters were determined by nonlinear regression on specific growth rates and various initial substrate concentrat-ions, and the values of the maximum specific growth rate, half saturation constant, and inhibition constant were 0.71 day?1, 34.3 mg L?1, and 183.5 mg L?1, respectively. This is the first report of ethylbenzene biodegradation by a bacterium of Microbacterium lacticum under nitrate-reducing conditions. 相似文献
70.