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61.
Van Anthony M. Villar John Edward Jones Ines Armando Laureano D. Asico Crisanto S. Escano Jr. Hewang Lee Xiaoyan Wang Yu Yang Annabelle M. Pascua-Crusan Cynthia P. Palmes-Saloma Robin A. Felder Pedro A. Jose 《The Journal of biological chemistry》2013,288(1):152-163
The peripheral dopaminergic system plays a crucial role in blood pressure regulation through its actions on renal hemodynamics and epithelial ion transport. The dopamine D5 receptor (D5R) interacts with sorting nexin 1 (SNX1), a protein involved in receptor retrieval from the trans-Golgi network. In this report, we elucidated the spatial, temporal, and functional significance of this interaction in human renal proximal tubule cells and HEK293 cells stably expressing human D5R and in mice. Silencing of SNX1 expression via RNAi resulted in the failure of D5R to internalize and bind GTP, blunting of the agonist-induced increase in cAMP production and decrease in sodium transport, and up-regulation of angiotensin II receptor expression, of which expression was previously shown to be negatively regulated by D5R. Moreover, siRNA-mediated depletion of renal SNX1 in C57BL/6J and BALB/cJ mice resulted in increased blood pressure and blunted natriuretic response to agonist in salt-loaded BALB/cJ mice. These data demonstrate a crucial role for SNX1 in D5R trafficking and that SNX1 depletion results in D5R dysfunction and thus may represent a novel mechanism for the pathogenesis of essential hypertension. 相似文献
62.
63.
青藏高原东缘常见种长毛风毛菊(Saussurea hieracioides)的繁殖分配 总被引:2,自引:0,他引:2
对分布在青藏高原东缘高寒草甸常见种长毛风毛菊的6个海拔梯度(3200~3850m)18个居群的繁殖分配进行了研究,结果表明:长毛风毛菊随海拔的升高个体和营养器官减小,繁殖的投入增加;随着海拔的升高,长毛风毛菊的个体管状小花数目和种子数目减少,管状小花重量和百粒重增大;个体管状小花的数目及重量和个体种子的数目及重量间存在权衡关系;长毛风毛菊的个体大小和繁殖分配存在负相关关系。在资源受限的环境下,长毛风毛菊以减少管状小花数目和种子的数目来增加管状小花重量和百粒重,是保证有性繁殖成功的策略之一。 相似文献
64.
Tutomu Masuda Mitsuko Yoshino Izumi Nishizaki Akira Tai Hiroshi Ozaki 《Bioscience, biotechnology, and biochemistry》2013,77(9):2199-2201
In order to elucidate the structure-activity relationship of griseofulvin (1), (±)-6′-demethyl analog (3), 2′-demethoxy-6′-demethyldihydro analog (4), (±)-dechloro-6′-ethyl analog (5), (±)-dechloro-6′-epi-ethyl analog (6), (±)-6′-ethyl analog (7) and (±)-6′-epi-ethyl analog (8) were synthesized by a Diels-Alder cycloaddition of alkylidene ketones (16, 17, 18, 19 and 20) with modified 1,3-butadienes (21 or 22). Their biological activities were examined against fungi. 相似文献
65.
目的:分析单眼远视性弱视儿童图形视觉诱发电位(P-VEP)检查情况,探讨外周发病机制,为临床诊疗提供依据。方法:选取2013年1月到2015年10月我院收治的单眼远视性弱视儿童75例(75只眼),另选取同期正常儿童32例(64只眼)为对照组,根据病情将弱视儿童分为轻度(A组)和对侧健眼组(B组),中度(C组)和对侧健眼组(D组),重度(E组)和对侧健眼组(F组),应用P-VEP检查各组P100波及振幅。结果:A组、C组、E组P100波潜伏期较B组、D组、F组和对照组延长(P0.05),振幅较B组、D组、F组和对照组降低(P0.05),A组、C组和、E组P100波潜伏期和振幅比较具有统计学意义(P0.05),B组、D组、F组P100波潜伏期与对照组无统计学意义(P0.05),B组、D组、F组振幅显著低于对照组(P0.05),B组、D组、F组P100波潜伏期和振幅比较无统计学意义(P0.05)。结论:单眼远视性弱视儿童弱视眼会出现P100波潜伏期延长,振幅降低,对侧健康眼会出现振幅降低。 相似文献
66.
Terrence L. Fisher Christine A. Reilly Laurie A. Winter Tracy Pandina Alan Jonason Maria Scrivens 《MABS-AUSTIN》2016,8(1):150-162
Semaphorin 4D (SEMA4D or CD100) is a member of the semaphorin family of proteins and an important mediator of the movement and differentiation of multiple cell types, including those of the immune, vascular, and nervous systems. Blocking the binding of SEMA4D to its receptors can result in physiologic changes that may have implications in cancer, autoimmune, and neurological disease. To study the effects of blocking SEMA4D, we generated, in SEMA4D-deficient mice, a panel of SEMA4D-specific hybridomas that react with murine, primate, and human SEMA4D. Utilizing the complementarity-determining regions from one of these hybridomas (mAb 67-2), we generated VX15/2503, a humanized IgG4 monoclonal antibody that is currently in clinical development for the potential treatment of various malignancies and neurodegenerative disorders, including multiple sclerosis and Huntington's disease. This work describes the generation and characterization of VX15/2503, including in vitro functional testing, epitope mapping, and an in vivo demonstration of efficacy in an animal model of rheumatoid arthritis. 相似文献
67.
Junichiro Futami Yuki Atago Akari Azuma Endy Widya Putranto Rie Kinoshita Hitoshi Murata Masakiyo Sakaguchi 《Biochemistry and Biophysics Reports》2016
It is now known that multicomponent protein assemblies strictly regulate many protein functions. The S100 protein family is known to play various physiological roles, which are associated with alternative complex formations. To prepare sufficient amounts of heterodimeric S100A8 and S100A9 proteins, we developed a method for bicistronic coexpression from a single-vector system using Escherichia coli cells as a host. The complex formation between S100A8 and S100A9 appears to be dependent on the thermodynamic stability of the protein during expression. The stable S100A8/A9 heterodimer complex spontaneously formed during coexpression, and biologically active samples were purified by cation-exchange chromatography. Semi-stable homodimers of S100A8 and S100A9 were also formed when expressed individually. These results suggest that the assembly of S100 protein complexes might be regulated by expression levels of partner proteins in vivo. Because protein assembly occurs rapidly after protein synthesis, coexpression of relevant proteins is crucial for the design of multicomponent recombinant protein expression systems. 相似文献
68.
Ning Gan Evgen Multia Heli Sirén Maija Ruuth Katariina Öörni Norbert M. Maier Matti Jauhiainen Marianna Kemell Marja-Liisa Riekkola 《Analytical biochemistry》2016
Immunoaffinity procedure was developed for isolation of low density lipoprotein (LDL) from biological samples by using silica-derived immunoaffinity sorbent. Sorbent was prepared by immobilization of monoclonal anti-apoB-100 antibody onto macroporous silica particles, using carefully optimized binding chemistry. Binding capacity of the sorbent towards LDL was determined by batch extraction experiments with solutions of isolated LDL in phosphate-buffered saline, and found to be 8 mg LDL/g. The bound LDL fraction was readily released from the sorbent by elution with ammonia at pH 11.2. The total time needed for isolation procedure was less than 1 h, with LDL recoveries being essentially quantitative for samples containing less than 0.3 mg LDL/mL. With higher concentrations, recoveries were less favorable, most probably due to irreversible adsorption caused by LDL aggreggation. However, reusability studies with isolated LDL at concentration 0.2 mg/mL indicate that the developed immunoaffinity material may be used for multiple binding-release cycles, with minor losses in binding capacity. Finally, the sorbent was successfully applied to isolation of LDL from diluted plasma. Apart from its practical implications for LDL isolation, this study provides crucial insights into issues associated with LDL-sorbent interactions, and may be useful in future efforts directed to development of lipoprotein isolation approaches. 相似文献
69.
70.
Franziska Foertsch Anna Szambowska Anja Weise Alexandra Zielinski Bernhard Schlott Florian Kraft 《Cell cycle (Georgetown, Tex.)》2016,15(20):2766-2779
The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is an essential process in maintenance of chromosomal stability. A key player of HR is the strand exchange factor RAD51 whose assembly at sites of DNA damage is tightly regulated. We detected an endogenous complex of RAD51 with the calcium-binding protein S100A11, which is localized at sites of DNA repair in HaCaT cells as well as in normal human epidermal keratinocytes (NHEK) synchronized in S phase. In biochemical assays, we revealed that S100A11 enhanced the RAD51 strand exchange activity. When cells expressing a S100A11 mutant lacking the ability to bind Ca2+, a prolonged persistence of RAD51 in repair sites and nuclear γH2AX foci was observed suggesting an incomplete DNA repair. The same phenotype became apparent when S100A11 was depleted by RNA interference. Furthermore, down-regulation of S100A11 resulted in both reduced sister chromatid exchange confirming the restriction of the recombination capacity of the cells, and in an increase of chromosomal aberrations reflecting the functional requirement of S100A11 for the maintenance of genomic stability. Our data indicate that S100A11 is involved in homologous recombination by regulating the appearance of RAD51 in DSB repair sites. This function requires the calcium-binding activity of S100A11. 相似文献