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1.
Reactive oxygen species (ROS) are involved in the pathophysiology of fulminant hepatic failure. Therefore, we developed polyethylene glycol-conjugated bovine serum albumin with multiple reduced thiols (PEG-BSA-SH) for the treatment of fulminant hepatic failure. As a long-circulating ROS scavenger, PEG-BSA-SH effectively scavenged highly reactive oxygen species and hydrogen peroxide in buffer solution. PEG-BSA-SH showed a long circulation time in the plasma after intravenous injection into mice. Fulminant hepatic failure was induced by intraperitoneal injection of lipopolysaccharide and d-galactosamine (LPS/d-GalN) into mice. The LPS/d-GalN-induced elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was significantly inhibited by a bolus intravenous injection of PEG-BSA-SH. Furthermore, the changes in hepatic lipid peroxide and hepatic blood flow were effectively suppressed by PEG-BSA-SH. In contrast, l-cysteine, glutathione, and dithiothreitol, three traditional reduced thiols, had no statistically significant effects on the serum levels of ALT or AST. These findings indicate that PEG-BSA-SH is a promising ROS scavenger and useful in the treatment of fulminant hepatic failure.  相似文献   
2.
In this study, a new lanthanum (III)-amino acid complex utilizing cysteine has been synthesized and characterized. The anticancer activities of the prepared La(III) complex against MCF-7 cell lines were studied. Results of MTT assay showed that at all three incubation times, the cytotoxic effect of prepared La(III) complex on MCF-7 breast cancer cell lines displays a time- and dose-dependent inhibitory effects. The interactions of the La(III) complex with two whey proteins (bovine serum albumin, BSA, and Bovine β-lactoglobulin, βLG) have been explored by using spectroscopic and molecular dicking methods. The obtained results indicated that La(III) complex strongly quenched the fluorescence of two carrier proteins in static quenching mode and also, BSA hah stronger binding affinity toward studied complex than βLG whit binding constant values of KBSA-La?Complex?~?0.11?×?104 M?1 and KβLG-La?Complex?~?0.63?×?103 M?1 at 300 K. The thermodynamic parameters revealed the contribution of hydrogen bond and Vander Waals interactions in both systems. The distances of the La(III) complex whit whey proteins were calculated using Förster energy transfer theory and proved existence of the energy transfer between two proteins and prepared La(III) complex with a high probability. FT-IR and UV–Vis absorption measurements indicated that the binding of the La(III) to BSA and βLG may induce conformational and micro-environmental changes of the proteins. The docking results indicate that the La(III) complex bind to residues located in the site II of BSA and second site of βLG.

Communicated by Ramaswamy H. Sarma  相似文献   

3.
Albumin is an abundant blood protein that acts as a transporter of a plethora of small molecules like fatty acids, hormones, toxins, and drugs. In addition, it has an unusual long serum half-life in humans of nearly 3 weeks, which is attributed to its interaction with the neonatal Fc receptor (FcRn). FcRn protects albumin from intracellular degradation via a pH-dependent cellular recycling mechanism. To understand how FcRn impacts the role of albumin as a distributor, it is of importance to unravel the structural mechanism that determines pH-dependent binding. Here, we show that although the C-terminal domain III (DIII) of human serum albumin (HSA) contains the principal binding site, the N-terminal domain I (DI) is important for optimal FcRn binding. Specifically, structural inspection of human FcRn (hFcRn) in complex with HSA revealed that two exposed loops of DI were in proximity with the receptor. To investigate to what extent these contacts affected hFcRn binding, we targeted selected amino acid residues of the loops by mutagenesis. Screening by in vitro interaction assays revealed that several of the engineered HSA variants showed decreased binding to hFcRn, which was also the case for two missense variants with mutations within these loops. In addition, four of the variants showed improved binding. Our findings demonstrate that both DI and DIII are required for optimal binding to FcRn, which has implications for our understanding of the FcRn-albumin relationship and how albumin acts as a distributor. Such knowledge may inspire development of novel HSA-based diagnostics and therapeutics.  相似文献   
4.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD begins with steatosis and advances to nonalcoholic steatohepatitis (NASH) and cirrhosis. The molecular mechanisms involved in NAFLD progression are not understood. Based on recent studies showing dysregulation of epidermal growth factor receptor (EGFR) in animal models of liver injury, we sought to determine if inhibition of EGFR mitigates liver fibrosis and HSC activation in NAFLD. We utilized the high fat diet (HFD)-induced murine model of liver injury to study the role of EGFR in NAFLD. The lipid accumulation, oxidative stress, hepatic stellate cell (HSC) activation and matrix deposition were examined in the liver tissues. We also evaluated the EGFR signaling pathway, ROS activation and pro-fibrogenic phenotype in oxidized low density lipoproteins (ox-LDL) challenged cultured HSCs. We demonstrate that EGFR was phosphorylated in liver tissues of HFD murine model of NAFLD. Inhibition of EGFR prevented diet-induced lipid accumulation, oxidative stress, and HSC activation and matrix deposition. In cultured HSCs, we show that ox-LDL caused rapid activation of the EGFR signaling pathway and induce the production of reactive oxygen species. EGFR also mediated HSC activation and promoted a pro-fibrogenic phenotype. In conclusion, our data demonstrate that EGFR plays an important role in NAFLD and is an attractive target for NAFLD therapy.  相似文献   
5.
The intracellular movement, following uptake of 125I-labelled denatured serum albumin into nonparenchymal liver cells, was followed by means of subcellular fractionation. Isolated nonparenchymal rat liver cells were prepared by means of differential centrifugation. The cells were homogenized in a sonifier and the cytoplasmic extract subjected to isopycnic centrifugation in a sucrose gradient. The intracellular movement of the labelled albumin was followed by comparing the distribution profile of radioactivity in the sucrose gradient with those of marker enzymes for plasma membrane and lysosomes. The distribution profiles for radioactivity after the cells had been exposed to the labelled denatured albumin for different time periods indicated that the radioactivity was first associated with subcellular fractions of lower modal densities than the lysosomes. With time of incubation the radioactivity moved towards higher densities. After prolonged incubations in the absence of extracellular labelled denatured albumin the radioactivity peak coincided with that of the lysosomal marker β-acetylglucosaminidase. When the cells were treated with the lysosomal inhibitor leupeptin, degradation of the labelled albumin was decreased, resulting in a massive intracellular accumulation of radioactivity. The radioactivity peak coincided with the peak of activity for the lysosomal marker β-acetylglucosaminidase, suggesting lysosomal degradation.  相似文献   
6.
The electrophoretic pattern of soluble proteins from seven rat brain regions (amygdala, cerebellum, corpus striatum, cortex, hypothalamus, medulla, and midbrain) was examined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Although the number of protein bands (36) was identical in all brain regions studied, there were differences in their relative densities, the greatest variation occurring in the low-molecular-weight region of the electrophoretogram. The bulk of the soluble proteins had molecular weights between 23,000 and 90,000 daltons. The medulla and amygdala showed the greatest range of protein band concentration. A large number of protein bands in the midbrain and corpus striatum showed a greater concentration of protein compared to the same bands in the other regions. A protein band that migrated with the same characteristic as albumin was found. It was consistently high in all regions, the midbrains showing a 1.5-fold greater concentration compared to other regions. Linear regression analysis of wet weight of regional brain tissue against protein concentration yielded a regression coefficient (r2) of 0.77. Midbrain and corpus striatum showed a relatively higher protein concentration: weight ratio than other regions.  相似文献   
7.
白蛋白与甲胎蛋白基因是由同一祖先基因进化而来。在小鼠,它们是一前一后定位在同一条染色体DNA上。在个体发育和肝癌变过程中,这两基因的相互关系也呈现相反的表达水平。因此,研究甲胎蛋白基因表达的调控与白蛋白基因是不可分割的。本文简要报道我们克隆了大鼠白蛋白mRNA 3′端顺序,为研究白蛋白基因结构和表达提供了必要的探针。白蛋白mRNA是从Wistar大鼠肝脏用双抗体免疫沉淀法提取。分子克隆技术基本是按“分子克隆”实验手册进行。  相似文献   
8.
In Mexican traditional medicine the plant species Bouvardia ternifolia is used as remedy to treat patients who have been stung by scorpions. In the preceding study, the methanol extract from the roots of this plant was capable of reducing the poisonous effect of Centruroides limpidus limpidus on mice. The poisoning from scorpion C. limpidus limpidus includes manifestations associated with the pancreatitis. This study evaluated the effect produced by the hexane and methanol extract from the root of B. ternifolia upon the acutely inflamed pancreas induced by the venom of C. limpidus limpidus on rats, and the release of amylase in the isolated pancreas of mice. The intravenous administration of venom induced the extravasation of labelled albumin, in a dose dependant manner. The pre-administration of both extracts of Bouvardia ternifolia reduced significantly (p < 0.05) the extravasation by 60%. Upon measuring the secretagogue effect of the venom in the isolated pancreas of mice, the EC50 of the venom was 3.76 x 10(-3) mg ml(-1), whilst in the presence of the methanol and hexane extracts, this EC50 was 9.13 x 10(-3) mg ml(-1) and 0.01629 mg ml(-1). In conclusion, the C. limpidus limpidus venom possesses a secretagogue effect of amylase on the pancreas of mice and produces an inflamed pancreas which is effectively antagonised by the hexane and methanol extracts from the roots of B. ternifolia.  相似文献   
9.
N. Harris  R. R. D. Croy 《Planta》1985,165(4):522-526
The major albumin protein in storage parenchyma tissue of developing peas has been localised at an ultrastructural level by immunocytochemistry. Tissue was fixed in buffered aldehyde and embedded in LR White resin which was polymerised by addition of catalyst. Sections were labelled by the indirect method of absorption of Protein A-gold to specifically bound antibodies. This method gives high levels of specific labelling on sections which retain good ultrastructural preservation and have high contrast after conventional staining. The albumin is located throughout the cytoplasm although no labelling was found associated with the endoplasmic reticulum, Golgi apparatus, vacuoles-protein bodies or other organelles.Abbreviation PMA pea major albumin protein  相似文献   
10.
原位椭圆偏振术研究牛血清清蛋白在固/液界面的吸附   总被引:1,自引:0,他引:1  
用原位椭圆偏振术系统研究了硅片表面因素及缓冲液环境因素对牛血清清蛋白在固/液界面吸附的影响。在生理条件下,疏水表面与亲水表面相比BSA吸附量较大。随着硅片表面电荷密度增加,BSA吸附量增加。BSA吸附量当体溶液pH值等于BSA等电点时达到最大。而随着体溶液离子强度增加,BSA吸附量亦上升。实验结果提示:除了熵驱动作用之外,硅片表面与BSA分子及BSA分子之间的静电作用在BSA吸附中起着十分重要的作用。  相似文献   
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