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131.
CHIP-mediated hyperubiquitylation of tau promotes its self-assembly into the insoluble tau filaments
Ji Hyeon Kim Jeeyoung Lee Won Hoon Choi Seoyoung Park Seo Hyeong Park Jung Hoon Lee Sang Min Lim Ji Young Mun Hyun-Soo Cho Dohyun Han Young Ho Suh Min Jae Lee 《Chemical science》2021,12(15):5599
The tau protein is a highly soluble and natively unfolded protein. Under pathological conditions, tau undergoes multiple post-translational modifications (PTMs) and conformational changes to form insoluble filaments, which are the proteinaceous signatures of tauopathies. To dissect the crosstalk among tau PTMs during the aggregation process, we phosphorylated and ubiquitylated recombinant tau in vitro using GSK3β and CHIP, respectively. The resulting phospho–ub-tau contained conventional polyubiquitin chains with lysine 48 linkages, sufficient for proteasomal degradation, whereas unphosphorylated ub-tau species retained only one–three ubiquitin moieties. Mass-spectrometric analysis of in vitro reconstituted phospho–ub-tau revealed seven additional ubiquitylation sites, some of which are known to stabilize tau protofilament stacking in the human brain with tauopathy. When the ubiquitylation reaction was prolonged, phospho–ub-tau transformed into insoluble hyperubiquitylated tau species featuring fibrillar morphology and in vitro seeding activity. We developed a small-molecule inhibitor of CHIP through biophysical screening; this effectively suppressed tau ubiquitylation in vitro and delayed its aggregation in cultured cells including primary cultured neurons. Our biochemical findings point to a “multiple-hit model,” where sequential events of tau phosphorylation and hyperubiquitylation function as a key driver of the fibrillization process, thus indicating that targeting tau ubiquitylation may be an effective strategy to alleviate the course of tauopathies.Multiple-hit model for tau aggregation, where sequential events of tau phosphorylation and hyperubiquitylation function as a key driver of the fibrillization process. 相似文献
132.
For large-volume stacking with the electroosmotic flow pump (LVSEP) in capillary electrophoresis of anionic analytes it is required that the electroosmotic mobility (EOM) should be smaller than the magnitudes of the effective mobilities of the analytes. When a fused-silica capillary is treated with an acidic solution, the silanoate group on the silica surface is neutralized to silanol and the EOM is suppressed. Due to the slow deprotonation equilibrium of the silanol group at an intermediate pH, this reduced EOM can be retained during a number of electrophoresis runs. Using a bare fused-silica capillary preconditioned with 0.01 M HCl, successful LVSEP at pH 6.0 was achieved for weakly acidic compounds with two orders of magnitude enhancements in the concentration sensitivity. The repeatability in migration times of ten analytes stacked by LVSEP in a single day was excellent with the relative standard deviation (RSD) less than 1% (n = 6). The day-to-day repeatability was also excellent with RSD less than 3% (n = 3 x 6) when the capillary was preconditioned each day. 相似文献
133.
W. Lyoo C. Park J. Yeum B. Ji C. Lee S. Lee J. Lee 《Colloid and polymer science》2002,280(12):1075-1083
To prepare ultrahigh molecular weight (UHMW) poly(vinyl pivalate) (PVPi) with high conversion and high linearity for a precursor of syndiotacticity-rich UHMW poly(vinyl alcohol) (PVA), vinyl pivalate (VPi) was suspension polymerized using a low-temperature initiator, 2,2'-azobis(2,4-dimethylvaleronitrile) (ADMVN), and the effects of polymerization conditions on the polymerization behavior and molecular structures of PVPi and PVA prepared by saponifying PVPi were investigated. Suspension polymerization was slightly inferior to bulk polymerization in increasing the molecular weight of PVA. In contrast, the former was superior in increasing the conversion of the polymer. Suspension polymerization of VPi at 25 °C by controlling various polymerization factors proved to be successful in obtaining PVA of UHMW (number-average degree of polymerization (Pn): 14,700-16,700), high syndiotactic diad content (62%), and of high yield (ultimate conversion of VPi into PVPi: 85-90%). In the case of bulk polymerization of VPi under the same conditions, maximum Pn, conversion of 15,800-17,000, and 25-35% were obtained, respectively. The degree of branching was lower and the Pn and syndiotacticity were higher with PVA prepared from PVPi polymerized at lower temperatures. All PVAs from PVPi suspension-polymerized at 25 °C were fibrous, with a high degree of crystallinity and orientation of the crystallites. 相似文献
134.
Hong J Kim YH Gil JH Cho K Jung JH Han SY 《Rapid communications in mass spectrometry : RCM》2002,16(22):2089-2093
The structural determination of sn-1 and sn-2 hexadecanoic lysophosphatidylcholine (LPC) regioisomers was carried out using fast atom bombardment tandem mass spectrometry (FAB-MS/MS). The collision-induced dissociation (CID) of protonated and sodiated molecules produced diverse product ions due mainly to charge remote fragmentations. Based on the information obtained from the CID spectra of protonated and sodiated molecules, sn-1 and sn-2 hexadecanoic LPC isomers could be discriminated. Especially, the abundance ratio of the diagnostic ion pair [m/z 224/226] in the CID spectra of [M + H](+) ions was shown to be greatly different. Moreover, the CID-MS/MS spectra of sodium-adducted molecules for hexadecanoic LPC isomers showed characteristic product ions such as [M + Na - 103](+), [M + Na - 85](+), and [M + Na - 59](+), by which their regio-specificity can be differentiated. 相似文献
135.
Proteomic analysis of colonic crypts from normal, multiple intestinal neoplasia and p53-null mice: a comparison with colonic polyps 总被引:5,自引:0,他引:5
In order to observe cellular changes caused by mutation of the tumor suppressors, APC and p53, we have generated protein expression profiles of mouse colon epithelial cells using two-dimensional electrophoresis (2-DE). Crypts, polyps and stroma were isolated from normal, multiple intestinal neoplasia (MIN) and p53-null mice, each with a C57Black/6J background, and subjected to 2-DE in two separate pH ranges (pH 3-10 and pH 6-11). No significant differences in protein expression patterns were observed between the normal, MIN and p53-null colon epithelial crypts. However, 64 proteins from the MIN polyps showed a 2-fold or greater difference in intensity that was statistically significant as assessed by the Wilcoxon rank-sum test (p < or = 0.05). Of these, calreticulin, carbonic anhydrase I and a new member of the glutathione-S-transferase theta family of proteins have so far been identified using an in-gel digestion protocol coupled with reversed-phase high performance liquid chromatography (RP-HPLC) ion-trap mass spectrometry. In addition, 38 marker proteins have been identified in a continuing effort to generate a comprehensive 2-DE database of proteins expressed by mouse colon epithelial cells (these databases are available at http://www.ludwig.edu.au/jpsl/jpslhome. html). 相似文献
136.
本文采用XE-60交联弹性石英性细管柱及407有机体埴充柱气色谱法可分分析丙烯腈中有机杂质。通过对柱长、担体粒度、液膜厚度、柱温和载气流量的选择。确定出最佳色 谱条件。 相似文献
137.
Xin Sheng Li Yan Xin Chen Yao Jun Zhang Chun Xin Ji Qin Xin 《Reaction Kinetics and Catalysis Letters》1996,58(2):391-396
Hydrogen adsorption-desorption over Mo2N has been studied using a temperature-programmed technique. It is revealed that hydrogen on Mo2N exhibits very high mobility leading to migration of the surface hydrogen into the sublayer and bulk of the sample or the reverse. The surface hydrogen species are preferentially formed when adsorption is carried out below 573 K. On increasing the adsorption temperature to above 573 K, the quantity of hydrogen species located in the sublayer or/and bulk of the Mo2N sample increases significantly. 相似文献
138.
漆树漆酶的催化氧化作用——Ⅳ.二茂铁及其衍生物的酶促氧化 总被引:2,自引:0,他引:2
In phosphate buffer-diethylene glycol monobutyl ether(DGBE), the oxidations of ferrocene and 15 derivatives were investigated in the presence of Rhus vernicifera laccase. The results showed that ferrocene and 11 derivatives can be oxidized. The mechanism of Laccase catalyzed oxidation of ferrocene was put forward. 相似文献
139.
140.
Klára Melánová Ludvík Beneš Vítězslav Zima Jan Svoboda Miroslava Trchová Jiří Dybal 《Journal of inclusion phenomena and macrocyclic chemistry》2007,58(1-2):95-101
Intercalation compounds of α-Zr(HPO4)2 · H2O with 1,2-alkanediols (from C3 to C16) have been prepared by replacing 1-propanol in α-Zr(HPO4)2 · 2C3H7OH with the desired 1,2-alkanediols by a treatment in a microwave field. It was found that the intercalates contain 1.5 molecules
of diol per formula unit. The diol molecules are placed between the host layers in a bimolecular way with their aliphatic
chains tilted at an angle of 51°. The diol molecules are anchored in the interlayer space by H-bonds. A mixed intercalate,
containing 1,2-butanediol and 1,2-decanediol in a roughly equimolar ratio, is formed when the α-Zr(HPO4)2 · 2C3H7OH intercalate, suspended in a mixture of 1,2-butanediol and 1,2-decanediol, is exposed to microwave radiation. No new phase
containing both types of the guest molecules was observed when the 1-propanol intercalate, suspended in a mixture of 1-propanol
and 1,2-octanediol, is exposed to microwave radiation. 相似文献