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991.
992.
多磷酸肌醇脂(这里指PIP和PIP2)的代谢在细胞信息传递和膜运转中起着重要的作用.脂多糖(lipopolysaccharide,LPS)于激活小鼠腹腔巨噬细胞(Mφ)初期(0.5~1h)和后期(16h)明显增加来自[γ-32P]ATP的32P参入Mφ的PIP和PIP2,32P参入PIP2的显著性大于PIP.LPS的这种作用在其激活Mφ的初期不受酪氨酸蛋白激酶抑制剂genistein、蛋白激酶A激动剂(forskolin)及百日咳毒素的影响;但佛波酯(PMA)长时间预处理的Mφ(其PKC活性被耗竭)再受LPS刺激,[32P]PIP2水平较LPS刺激未受PMA预处理的Mφ明显降低.结果表明,LPS于激活Mφ的初期和后期更显著增加PI4P-5激酶的活性,导致PIP2合成增加,PIP2合成的增加可能与Mφ激活时不同时期所表达的功能相关. 相似文献
993.
Cao Yongxian Zhang Feng Wang Haotian Bi Chunhua Cui Jinpeng Liu Fenghai Pan Huazheng 《Molecular and cellular biochemistry》2021,476(1):279-292
Molecular and Cellular Biochemistry - Drug resistance is one of the major challenges for cancer therapies. In recent years, research on disease-related molecular signaling pathways has become the... 相似文献
994.
The cold-active lipase gene Lip-948, cloned from Antarctic psychrotrophic bacterium Psychrobacter sp. G, was ligated into plasmid pColdI. The recombinant plasmid pColdI+Lip-948 was then transformed into Escherichia coli BL21. SDS-PAGE analysis showed that there was substantive expression of lipase LIP-948 in E. coli with a yield of about 39% of total protein, most of which was present in the inclusion body. The soluble protein LIP-948 only consisted of 1.7% of total LIP-948 with a specific activity of 66.51U/mg. Co-expression of molecular chaperones with the pColdI+Lip-948 were also carried out. The results showed that co-expression of different chaperones led to an increase or decrease in the formation of soluble LIP-948 in varying degrees. Co-expression of pColdI+Lip-948 with chaperone pTf16 and pGro7 decreased the amount of soluble LIP-948, while the soluble expression was enhanced when pColdI+Lip-948 was co-expressed with "chaperone team" plasmids (pKJE7, pG-Tf2, pG-KJE8), respectively. LIP-948 was most efficiently expressed in soluble form when it was co-expressed with pG-KJE8, which was up to 19.8% of intracellular soluble proteins and with a specific activity of 108.77U/mg. The soluble LIP-948 was purified with amylase affinity chromatography and its enzymatic characters were studied. The optimal temperature and pH of LIP-948 was 35°C and 8, respectively. The activity of LIP-948 dropped dramatically after incubation at 50°C for 15min and was enhanced by Sr(2+), Ca(2+). It preferentially hydrolyzed 4-nitrophenyl esters with the shorter carbon chain. 相似文献
995.
996.
Cong Yu Shang Cui Chen Zong Weina Gao Tongfu Xu Peng Gao Jicui Chen Dandan Qin Qingbo Guan Yuantao Liu Yuchang Fu Xia Li Xiangdong Wang 《The Journal of biological chemistry》2015,290(34):20687-20699
The role of NR4A1 in apoptosis is controversial. Pancreatic β-cells often face endoplasmic reticulum (ER) stress under adverse conditions such as high free fatty acid (FFA) concentrations and sustained hyperglycemia. Severe ER stress results in β-cell apoptosis. The aim of this study was to analyze the role of NR4A1 in ER stress-mediated β-cell apoptosis and to characterize the related mechanisms. We confirmed that upon treatment with the ER stress inducers thapsigargin (TG) or palmitic acid (PA), the mRNA and protein levels of NR4A1 rapidly increased in both MIN6 cells and mouse islets. NR4A1 overexpression in MIN6 cells conferred resistance to cell loss induced by TG or PA, as assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and TUNEL assays indicated that NR4A1 overexpression also protected against ER stress-induced apoptosis. This conclusion was further confirmed by experiments exploiting siRNA to knockdown NR4A1 expression in MIN6 cells or exploiting NR4A1 knock-out mice. NR4A1 overexpression in MIN6 cells reduced C/EBP homologous protein (CHOP) expression and Caspase3 activation induced by TG or PA. NR4A1 overexpression in MIN6 cells or mouse islets resulted in Survivin up-regulation. A critical regulatory element was identified in Survivin promoter (−1872 bp to −1866 bp) with a putative NR4A1 binding site; ChIP assays demonstrated that NR4A1 physically associates with the Survivin promoter. In conclusion, NR4A1 protects pancreatic β-cells against ER stress-mediated apoptosis by up-regulating Survivin expression and down-regulating CHOP expression, which we termed as “positive and negative regulation.” 相似文献
997.
A 3D sodium(I) complex driven by the coordination bonds and a 3D hydrogen-bond-sustained network, with empirical formulae [Na2(3,5-pdc)(H2O)4]n (1) and [Na2(4-pc)2(H2O)8]n (2), respectively, have been synthesized and characterized. X-ray single crystal determination of 1 reveals that two types of hexa-coordinate sodium(I) ions are alternately arranged through three double μ2-OH2 bridges and one double μ2 oxygen bridge coming from one carboxylic oxygen atom of a 3,5-pdc ligand. In comparison to 1, only one kind of six-coordinate sodium ions in octahedral coordination configurations is bridged by double μ2 aqua bridges in 2 forming a straight line via the similar Na-Na separations. In addition, the fixation of coordinating bonds around the sodium centers in 1 makes pyridine rings parallel to each other and the centroid-centroid separation of 3.539 Å, while in complex 2 pyridine rings are arranged more flexibly merely by the hydrogen bonding interactions associated with its nitrogen atom and a carboxylic group. To the best of our knowledge, 1 is the first 3D framework sustained only by coordination interactions between alkali metals and carboxylates. It is also noted that two types of hexa-coordinate sodium(I) centers are present in complex 1 at the same time and two kinds of topologies (zig-zag and ring) are produced. Complex 2 is an unprecedented 3D sodium(I) network sustained by the hydrogen bonding and the π-π interactions in the absence of coordination forces. 相似文献
998.
999.
Arginine 352 (R352) in the sixth transmembrane domain of the cystic fibrosis transmembrane conductance regulator (CFTR) previously
was reported to form an anion/cation selectivity filter and to provide positive charge in the intracellular vestibule. However,
mutations at this site have nonspecific effects, such as inducing susceptibility of endogenous cysteines to chemical modification.
We hypothesized that R352 stabilizes channel structure and that charge-destroying mutations at this site disrupt pore architecture,
with multiple consequences. We tested the effects of mutations at R352 on conductance, anion selectivity and block by the
sulfonylurea drug glipizide, using recordings of wild-type and mutant channels. Charge-altering mutations at R352 destabilized
the open state and altered both selectivity and block. In contrast, R352K-CFTR was similar to wild-type. Full conductance
state amplitude was similar to that of wild-type CFTR in all mutants except R352E, suggesting that R352 does not itself form
an anion coordination site. In an attempt to identify an acidic residue that may interact with R352, we found that permeation
properties were similarly affected by charge-reversing mutations at D993. Wild-type-like properties were rescued in R352E/D993R-CFTR,
suggesting that R352 and D993 in the wild-type channel may interact to stabilize pore architecture. Finally, R352A-CFTR was
sensitive to modification by externally applied MTSEA+, while wild-type and R352E/D993R-CFTR were not. These data suggest that R352 plays an important structural role in CFTR,
perhaps reflecting its involvement in forming a salt bridge with residue D993. 相似文献
1000.
In plant genomes, the function of a substantial percentage of the putative protein-coding open reading frames (ORFs) is unknown. These ORFs have no significant sequence similarity to known proteins, which complicates the task of functional study of these proteins. Efforts are being made to explore methods that are complementary to, or may be used in combination with, sequence alignment and clustering methods. A web-based protein functional class prediction software, SVMProt, has shown some capability for predicting functional class of distantly related proteins. Here the usefulness of SVMProt for functional study of novel plant proteins is evaluated. To test SVMProt, 49 plant proteins (without a sequence homolog in the Swiss-Prot protein database, not in the SVMProt training set, and with functional indications provided in the literature) were selected from a comprehensive search of MEDLINE abstracts and Swiss-Prot databases in 1999-2004. These represent unique proteins the function of which, at present, cannot be confidently predicted by sequence alignment and clustering methods. The predicted functional class of 31 proteins was consistent, and that of four other proteins was weakly consistent, with published functions. Overall, the functional class of 71.4% of these proteins was consistent, or weakly consistent, with functional indications described in the literature. SVMProt shows a certain level of ability to provide useful hints about the functions of novel plant proteins with no similarity to known proteins. 相似文献