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101.
Post‐translational modifications of transthyretin affect the triiodonine‐binding potential
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Andrea Henze Thomas Homann Mustafa Serteser Ozge Can Ozlem Sezgin Abdurrahman Coskun Ibrahim Unsal Florian J. Schweigert Aysel Ozpinar 《Journal of cellular and molecular medicine》2015,19(2):359-370
Transthyretin (TTR) is a visceral protein, which facilitates the transport of thyroid hormones in blood and cerebrospinal fluid. The homotetrameric structure of TTR enables the simultaneous binding of two thyroid hormones per molecule. Each TTR subunit provides a single cysteine residue (Cys10), which is frequently affected by oxidative post‐translational modifications. As Cys10 is part of the thyroid hormone‐binding channel within the TTR molecule, PTM of Cys10 may influence the binding of thyroid hormones. Therefore, we analysed the effects of Cys10 modification with sulphonic acid, cysteine, cysteinylglycine and glutathione on binding of triiodothyronine (T3) by molecular modelling. Furthermore, we determined the PTM pattern of TTR in serum of patients with thyroid disease by immunoprecipitation and mass spectrometry to evaluate this association in vivo. The in silico assays demonstrated that oxidative PTM of TTR resulted in substantial reorganization of the intramolecular interactions and also affected the binding of T3 in a chemotype‐ and site‐specific manner with S‐glutathionylation as the most potent modulator of T3 binding. These findings were supported by the in vivo results, which indicated thyroid function‐specific patterns of TTR with a substantial decrease in S‐sulphonated, S‐cysteinylglycinated and S‐glutathionylated TTR in hypothyroid patients. In conclusion, this study provides evidence that oxidative modifications of Cys10 seem to affect binding of T3 to TTR probably because of the introduction of a sterical hindrance and induction of conformational changes. As oxidative modifications can be dynamically regulated, this may represent a sensitive mechanism to adjust thyroid hormone availability. 相似文献
102.
Jie Cheng Miook Cho Jin-ming Cen Meng-yun Cai Shun Xu Ze-wei Ma Xinguang Liu Xi-li Yang Can Chen Yousin Suh Xing-dong Xiong 《PloS one》2015,10(2)
SIRT1 exerts protective effects against endothelial cells dysfunction, inflammation and atherosclerosis, indicating an important role on myocardial infarction (MI) pathogenesis. Nonetheless, the effects of SIRT1 variants on MI risk remain poorly understood. Here we aimed to investigate the influence of SIRT1 polymorphisms on individual susceptibility to MI. Genotyping of three tagSNPs (rs7069102, rs3818292 and rs4746720) in SIRT1 gene was performed in a Chinese Han population, consisting of 287 MI cases and 654 control subjects. In a logistic regression analysis, we found that G allele of rs7069102 had increased MI risk with odds ratio (OR) of 1.57 [95% confidence interval (CI) = 1.15–2.16, Bonferroni corrected P (Pc) = 0.015] after adjustment for conventional risk factors compared to C allele. Similarly, the combined CG/GG genotypes was associated with the increased MI risk (OR = 1.64, 95% CI = 1.14–2.35, Pc = 0.021) compared to the CC genotype. Further stratified analysis revealed a more significant association with MI risk among younger subjects (≤ 55 years old). Consistent with these results, the haplotype rs7069102G-rs3818292A-rs4746720T containing the rs7069102 G allele was also associated with the increased MI risk (OR = 1.41, 95% CI = 1.09–1.84, Pc = 0.040). However, we did not detect any association of rs3818292 and rs4746720 with MI risk. Our study provides the first evidence that the tagSNP rs7069102 and haplotype rs7069102G-rs3818292A-rs4746720T in SIRT1 gene confer susceptibility to MI in the Chinese Han population. 相似文献
103.
104.
Construction of a Bacillus thuringiensis engineered strain with high toxicity and broad pesticidal spectrum against coleopteran insects 总被引:1,自引:0,他引:1
Jingjing Liu Guixin Yan Changlong Shu Can Zhao Chunqin Liu Fuping Song Lin Zhou Junlan Ma Jie Zhang Dafang Huang 《Applied microbiology and biotechnology》2010,87(1):243-249
A newly engineered strain, denominated BIOT185, was constructed through integrating the cry8Ca2 gene into the endogenous plasmid of BT185 (contains cry8Ea1) by homologous recombination. The thermosensitive plasmid vector was eliminated by the rising temperature of recombinant
cultures. No antibiotic gene or other unnecessary genes were introduced to the new strain. Sodium dodecyl sulfate–polyacrylamide
gel electrophoresis and Western blot analysis demonstrated that the cry8Ca2 gene was expressed normally and produced a 130-kDa protein in the BIOT185 strain. Bioassay results showed that the new strain
had high toxicity to the pests Anomala corpulenta and Holotrichia parallela, which often damage the same fields. 相似文献
105.
Britt-Marie Swahn David Wensbo Johan Sandell Daniel Sohn Can Slivo David Pyring Jonas Malmström Erwan Arzel Michaela Vallin Margareta Bergh Fredrik Jeppsson Allan E. Johnson Anders Juréus Jan Neelissen Samuel Svensson 《Bioorganic & medicinal chemistry letters》2010,20(6):1976-1980
The syntheses and SAR of new series of β-amyloid binding agents are reported. The effort to optimize signal-to-background ratios for these ligands are described. Compounds 8, 21 and 30 displayed desirable lipophilicity and pharmacokinetic properties. Compounds 8 and 21 were evaluated with in vitro autoradiographic studies and in vivo in APP/PS1 transgenic mice. It is shown that it was possible to increase the signal-to-background ratios compared to PIB 1, as demonstrated by compounds 8 and 21. 相似文献
106.
Betul Can Gulnihal Kulaksiz Erkmen Ozlem Dalmizrak I. Hamdi Ogus Nazmi Ozer 《The protein journal》2010,29(4):250-256
Glutathione reductase [GR, E.C.1.8.1.7] catalyses NADPH dependent reduction of glutathione disulfide (GSSG) to reduced glutathione
(GSH). Thus, it is the crucial enzyme to maintain high [GSH]/[GSSG] ratio and physiological redox status in cells. Kidney
and liver tissues were considered as a rich source of GR. In this study, rat kidney GR was purified and some of its properties
were investigated. The enzyme was purified 2,356 fold with a yield of 16% by using heat-denaturation and Sephadex G25 gel
filtration, 2′,5′-ADP Agarose 4B, PBE94 column chromatographies. The purified enzyme had a specific activity (Vm) of 250 U/mg protein and the ratio of absorbances at wavelengths of A
273/A
463,
A
280/A
460, A
365/A
460, and A
379/A
463, were 7.1, 6.8, 1.2 and 1.0, respectively. Each mol of GR subunit bound 0.97 mol of FAD. NADH was used as a coenzyme by rat
kidney GR but with a lower efficiency (32.7%) than NADPH. Its subunit molecular weight was estimated as 53 kDa. An optimum
pH of 6.5 and optimum temperature of 65 °C were found for rat kidney GR. Its activation energy (Ea) and temperature coefficient
(Q10) were calculated as 7.02 kcal/mol and 1.42, respectively. The Km(NADPH) and kcat/Km (NADPH) values were found to be 15.3 ± 1.4 μM and 1.68 × 107 M−1 s−1 for the concentration range of 10-200 μM NADPH and when GSSG is the variable substrate, the Km(GSSG) and the kcat/Km(GSSG) values of 53.1 ± 3.4 μM and 4.85 × 106 M−1 s−1 were calculated for the concentration range of 20–1,200 μM GSSG. 相似文献
107.
108.
Lijuan Chen Yi Zhang Lin Tang Danlian Huang Can Liu Ya Pang Jie Luo 《Analytical biochemistry》2010,407(2):172-179
Picloram, a herbicide widely used for broadleaf weed control, is persistent and mobile in soil and water with adverse health and environmental effects. It is important to develop a sensitive method for accurate detection of trace picloram in the environment. In this article, a type of ordered three-dimensional (3D) gold (Au) nanoclusters obtained by two-step electrodeposition using the spatial obstruction/direction of the polycarbonate membrane is reported. Bovine serum albumin (BSA)-picloram was immobilized on the 3D Au nanoclusters by self-assembly, and then competitive immunoreaction with picloram antibody and target picloram was executed. The horseradish peroxidase (HRP)-labeled secondary antibody was applied for enzyme-amplified amperometric measurement. The electrodeposited Au nanoclusters built direct electrical contact and immobilization interface with protein molecules without postmodification and positioning. Under the optimal conditions, the linear range for picloram determination was 0.001-10 μg/ml with a correlation coefficient of 0.996. The detection and quantification limits were 5.0 × 10−4 and 0.0021 μg/ml, respectively. Picloram concentrations in peach and excess sludge supernatant extracts were tested by the proposed immunosensor, which exhibited good precision, sensitivity, selectivity, and storage stability. 相似文献
109.
糖尿病肾病(DN)是糖尿病(DM)最常见的慢性并发症,也是终末期肾病(ESRD)的主要原因,其治疗费用巨大。其发病机制主要涉及遗传易感性、糖代谢紊乱、肾血流动力学的改变、细胞因子、炎症机制已及氧化应激等方面。本文就以上作用机制的最新研究进展作一综述。 相似文献
110.