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91.
The heparin‐binding domain of HB‐EGF as an efficient cell‐penetrating peptide for drug delivery 下载免费PDF全文
Zhao Luo Xue‐Wei Cao Chen Li Miao‐Dan Wu Xu‐Zhong Yang Jian Zhao Fu‐Jun Wang 《Journal of peptide science》2016,22(11-12):689-699
Cell‐penetrating peptides (CPPs) have been shown to be potential drug carriers for cancer therapy. The inherently low immunogenicity and cytotoxicity of human‐derived CPPs make them more suitable for intracellular drug delivery compared to other delivery vehicles. In this work, the protein transduction ability of a novel CPP (termed HBP) derived from the heparin‐binding domain of HB‐EGF was evaluated. Our data shows, for the first time, that HBP possesses similar properties to typical CPPs and is a potent drug delivery vector for improving the antitumor activity of impermeable MAP30. The intrinsic bioactivities of recombinant MAP30‐HBP were well preserved compared to those of free MAP30. Furthermore, HBP conjugated to the C‐terminus of MAP30 promoted the cellular uptake of recombinant MAP30‐HBP. Moreover, the fusion of HBP to MAP30 gave rise to significantly enhanced cytotoxic effects in all of the tumor cell lines tested. In HeLa cells, this cytotoxicity was mainly caused by the induction of cell apoptosis. Further investigation revealed that HBP enhanced MAP30‐induced apoptosis through the activation of the mitochondrial‐ and death receptor‐mediated signaling pathways. In addition, the MAP30‐HBP fusion protein caused more HeLa cells to become arrested in S phase compared to MAP30 alone. These results highlight the MAP30‐HBP fusion protein as a promising drug candidate for cancer therapy and demonstrate HBP, a novel CPP derived from human HB‐EGF, as a new potential vector for antitumor drug delivery. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
92.
目的:探索辛伐他汀联合低分子肝素对慢性心力衰竭(CHF)患者的D-二聚体、N-末端脑钠肽前体(NT-proBNP)、左室射血分数(LVEF)、左室舒末内径、血清反应蛋白(CRP)、血浆纤维蛋白原(FB)、血清总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)的影响。方法:选择我院自2010年4月至2014年7月间收治的患有CHF患者80例,按照随机数表法分成治疗组和对照组,各40例。两组均给予常规治疗,治疗组在常规治疗的基础上加用辛伐他汀和低分子肝素,治疗两个月。对比两组患者治疗前后D-二聚体、NT-proBNP、LVEF、左室舒末内径、CRP、FB、TC和LDL-C水平。结果:与治疗前相比,对照组患者治疗后的D-二聚体、NT-proBNP、LVEF、左室舒末内径、CRP、FB、TC和LDL-C水平均无明显改善,而治疗组患者上述各项指标均显著改善,差异均具有统计学意义(均P0.05)。结论:临床上应用辛伐他汀联合低分子肝素可以有效改善CHF患者的相关指标,对于疾病的治疗具有重要作用,值得在临床上应用及推广。 相似文献
93.
Characterization of tumors produced by signal peptide-basic fibroblast growth factor-transformed cells 总被引:2,自引:0,他引:2
Basic fibroblast growth factor (bFGF) is found in a variety of cells and tissues. We have previously shown that bFGF is a transforming growth factor, but only when fused to a signal peptide (sp-bFGF). Cells expressing the native bFGF are tumorigenic in nude mice only, where the tumors form at a low frequency and grow very slowly as compared to sp-bFGF tumors. The cells transformed by the sp-bFGF growth factor gene cause rapidly growing tumors within 10 days in 100% of syngeneic and nude mice. In nude mice, the tumors are highly vascularized, while the vascularization in immunocompetent syngeneic mice is not as prominent. The syngeneic mice have a characteristic humoral immune response to sp-bFGF tumors, which differs from that mounted against ras-induced tumors. The ability of bFGF to induce tumorigenicity is significant in view of the recent discoveries of three new oncogenes: hst, int-2, and an oncogene from a human colon cancer. In addition to homology with FGF, the proteins encoded by these oncogenes all have a potential signal peptide at the protein's amino terminus, suggesting a mode of action analogous to that of our artificial signal peptide-bFGF (sp-bFGF) transforming growth factor model system. 相似文献
94.
Oocyte maturation-preventing factor (OMPF) was extracted from bovine granulosa cells with a buffer containing 1 M urea and 5 mM EDTA. OMPF was partially purified by gel filtration on Sephadex G25 and by reversed-phase high performance liquid chromatography. The maturation-preventing activity of purified fractions was determined by measuring their capacity to block the spontaneous dissolution of the germinal vesicle (GVBD) of isolated cumulus-enclosed mouse oocytes. Hyaluronic acid, chondroitin sulfate, heparin, heparan sulfate, keratan sulfate, and dextran sulfate at concentrations of 500 μg/ml did not affect the frequency of GVBD of isolated mouse oocytes. Heparin and heparan sulfate, however, blocked the inhibitory effect of OMPF, whereas the inhibition of GVBD induced with dibutyryl cAMP, forskolin, W7 (calmodulin antagonist), and 3-isobutyl-l-methylxanthine (phosphodiesterase inhibitor) was not blocked. OMPF was eluted in the adsorbed fraction when chromatographed on heparin-Agarose, showing interaction of OMPF with heparin. The present results suggest that the glycosaminoglycan matrix may influence OMPF action on oocytes. 相似文献
95.
Modifications of low-density lipoprotein induced by arterial proteoglycans and chondroitin-6-sulfate
Germán Camejo Eva Hurt Olov Wiklund Birgitta Rosengren Flor López Göran Bondjers 《生物化学与生物物理学报:疾病的分子基础》1991,1096(3):253-261
Association of low-density lipoproteins (LDL) with arterial chondroitin sulfate proteoglycans (CSPG) appears to contribute to their deposition in the extracellular intimal compartment and to its internalization by macrophages. CSPG and LDL interact by ionic bridges with formation of soluble and insoluble complexes. We studied the alterations on LDL structure induced by its association with arterial CSPG and other glycosaminoglycans (GAG). In soluble complexes, at low and physiological ionic strength, arterial CSPG and sulfated GAG modify the kinetics of apoB-100 proteolysis by trypsin. However, less marked alterations in the peptide patterns were observed with proteinase V8 and almost none with thermolysin. This is indirect evidence that the presence of CSPG and GAG modified the exposure of polar regions of apoB-100 in LDL. Competitive binding experiments with agarose-bound heparin and soluble GAG also suggest that after formation of insoluble complexes with arterial CSPG and resolubilization the exposure of Lys, Arg-rich segments of apoB-100 is increased. Results from differential scanning calorimetry and differential thermal spectrophotometry showed that the CSPG and GAG-induced modifications reduced the thermal stability of the surface and core in LDL. If present in vivo, the structural alterations of polar segments of the LDL protein moiety may influence the outcome of its alteration with the arterial mesenchyma. 相似文献
96.
牵拉猫左心房所致的肾效应 总被引:1,自引:0,他引:1
本实验在50只麻醉猫中研究了牵拉左心房(LAS)对尿量(UV)、尿钠(U_(Na)V)和尿钾(U_KV)排出量的影响。在迷走神经完整的动物,LAS 导致 UV,U_(Na)V 和 U_KV(P<0.001)明显增加。切断迷走神经后 LAS 仍能使 UV,U_(Na)V 有所增加(p<0.01),但增加量明显低于迷走神经完整的动物(P<0.005)。在迷走神经完整的猫滴注肝素(10U/min/mg)后,LAS 也能引起 UV,U_(Na)V 和 U_KV 的增加,但增值明显低于没有滴注肝素的猫。在迷走神经切除后滴入肝素,则 LAS 的肾效应消失(p>0.05)。切断左侧肾神经后,LAS 引起神经完整肾尿量和尿钠排出显著增加(P<0.001)。而去神经肾对 LAS 的效应虽减弱,但其增值仍有显著性。两侧肾效应的差异,在统计学上是显著的(P<0.05)。上述结果说明,LAS 在麻醉猫中能引起尿量,尿钠和尿钾明显增加,这些效应是神经反射和体液机制共同作用的结果。 相似文献
97.
Heparin of an average molecular weight of 13,000 was fractionated on the basis of size into five fractions of different weight-average molecular weight ranging from 8500 to 20,000. The heparin was also degraded using microbial heparinase resulting in products ranging from a disaccharide of molecular weight 500 to an oligosaccharide of molecular weight 3100. These products were also size fractionated. The individual heparin fractions and products were tested for metachromatic activity with Azure A. The metachromatic activity of the heparin fractions was independent of molecular weight, while the metachromatic activity of the products was dependent on molecular weight. Metachromatic activity was found in a fragment as small as a tetrasaccharide. Anticoagulant activity was found in fragments of tetrasaccharide or larger by a Factor Xa clotting assay and in fragments of hexasaccharide or larger by a Factor Xa amidolytic chromogenic assay. 相似文献
98.
T.N. Huckerby I.A. Nieduszynski 《International journal of biological macromolecules》1982,4(5):269-274
Data are presented for 13C spin-lattice (T1) relaxation times and nuclear Overhauser enhancement (NOE) values in a range of heparinoid glycosaminoglycans. These paramaters are compared with T1and NOE values for simple dextrans of . For the heparinoid molecules, significant and consistent differences in relaxation times are observed for different ring carbons, for which simple models do not provide an adequate explanation. No such variations are found for the dextrans. Both families of polysaccharides exhibit NOE values significantly reduced from the theoretical maximum. These changes are discussed in terms of molecular rotational correlation times (τc) which are similar in magnitude to the resonance frequencies used for n.m.r. measurements. It is concluded that for the n.m.r. investigation of polysaccharides at high field strengths () considerable economy of time will be achieved by the use of INEPT experiments rather than conventional Overhauser signal enhancement via proton-noise decoupling. 相似文献
99.
100.
Hinke A. B. Multhaupt John R. Couchman 《The journal of histochemistry and cytochemistry》2012,60(12):908-915
Heparan sulfate is perhaps the most complex polysaccharide known from animals. The basic
repeating disaccharide is extensively modified by sulfation and uronic acid epimerization.
Despite this, the fine structure of heparan sulfate is remarkably consistent with a
particular cell type. This suggests that the synthesis of heparan sulfate is tightly
controlled. Although genomics has identified the enzymes involved in glycosaminoglycan
synthesis in a number of vertebrates and invertebrates, the regulation of the process is
not understood. Moreover, the localization of the various enzymes in the Golgi apparatus
has not been carried out in a detailed way using high-resolution microscopy. We have begun
this process, using well-known markers for the various Golgi compartments, coupled with
the use of characterized antibodies and cDNA expression. Laser scanning confocal
microscopy coupled with line scanning provides high-quality resolution of the distribution
of enzymes. The EXT2 protein, which when combined as heterodimers with EXT1 comprises the
major polymerase in heparan sulfate synthesis, has been studied in depth. All the data are
consistent with a cis-Golgi distribution and provide a starting point to establish whether
all the enzymes are clustered in a multimolecular complex or are distributed through the
various compartments of the Golgi apparatus. 相似文献