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61.
The NET [noradrenaline (norepinephrine) transporter], an Na+/Cl--dependent neurotransmitter transporter, has several isoforms produced by alternative splicing in the C-terminal region, each differing in expression and function. We characterized the two major isoforms of human NET, hNET1, which has seven C-terminal amino acids encoded by exon 15, and hNET2, which has 18 amino acids encoded by exon 16, by site-directed mutagenesis in combination with NE (noradrenaline) uptake assays and cell surface biotinylation. Mutants lacking one third or more of the 24 amino acids encoded by exon 14 exhibited neither cell surface expression nor NE uptake activity, with the exception of the mutant lacking the last eight amino acids of hNET2, whose expression and uptake resembled that of the WT (wild-type). A triple alanine replacement of a candidate motif (ENE) in this region mimicked the influences of the truncation. Deletion of either the last three or another four amino acids of the C-terminus encoded by exon 15 in hNET1 reduced the cell surface expression and NE uptake, whereas deletion of all seven residues reduced the transport activity but did not affect the cell surface expression. Replacement of RRR, an endoplasmic reticulum retention motif, by alanine residues in the C-terminus of hNET2 resulted in a similar expression and function compared with the WT, while partly recovering the effects of the mutation of ENE. These findings suggest that in addition to the function of the C-terminus, the common proximal region encoded by exon 14 regulates the functional expression of splice variants, such as hNET1 and hNET2. 相似文献
62.
Nishizawa R Nishiyama T Hisaichi K Matsunaga N Minamoto C Habashita H Takaoka Y Toda M Shibayama S Tada H Sagawa K Fukushima D Maeda K Mitsuya H 《Bioorganic & medicinal chemistry letters》2007,17(3):727-731
Hydroxylated derivatives were designed and synthesized based on the information of oxidative metabolites. Compounds derived from beta-substituted (2R,3R)-2-amino-3-hydroxypropionic acid showed improved inhibitory activities against the binding of MIP-1alpha to human CCR5, compared with the non-hydroxylated derivatives and the other isomers. 相似文献
63.
Removal characteristics of metal ions using degreased coffee beans: adsorption equilibrium of cadmium(II) 总被引:1,自引:0,他引:1
The feasibility of using coffee beans after being dripped and degreased (DCB) as an adsorbent for base metals such as copper(II), zinc(II), lead(II), iron(III) and cadmium(II) were examined. The compositions of the DCB were characterized by Fourier transform infrared spectroscopy, scanning electronic micrograph and fluorescent X-ray. It was found that DCB contain sulfur and calcium from the analysis using fluorescent X-ray. The plant cell wall in DCB has the porous structure from the scanning electron microscopy (SEM) analysis, and the specific surface area was determined to be 1.2 m2/g using the specific surface area analyzer. Batch adsorption experiments on DCB were carried out at various pHs in order to elucidate the selectivity of metal ions. All metals were adsorbed at low pH region (3.0-5.0). Of particular interest was the adsorption characteristics of cadmium(II) on DCB. The adsorption isotherm for cadmium(II) at pH 8 fitted with a Langmuir equation to yield an adsorption equilibrium constant of 55.2 mmol dm(-3) and an adsorption capacity of 5.98 x 10(-2) mmol g(-1). The desorption of cadmium(II) was easily achieved over 90% by a single batchwise treatment with an aqueous solution of hydrochloric acid or nitric acid at more than 0.01 mol dm(-3). These results suggested that DCB behaves as a cation exchanger. 相似文献
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65.
Effects of adiponectin on the renal sympathetic nerve activity and blood pressure in rats 总被引:2,自引:0,他引:2
Tanida M Shen J Horii Y Matsuda M Kihara S Funahashi T Shimomura I Sawai H Fukuda Y Matsuzawa Y Nagai K 《Experimental biology and medicine (Maywood, N.J.)》2007,232(3):390-397
Adiponectin is an adipocytokine that modulates energy homeostasis and glucose metabolism. Here, we examined the effects of acute intravenous (iv) and lateral cerebral ventricular (LCV) injections of adiponectin on the renal sympathetic nerve activity (RSNA) and blood pressure (b/p) in urethane-anesthetized rats. Both iv and LCV injections of adiponectin induced dose-dependent suppressions of RSNA and b/p. Moreover, we found that bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) abolished the effects of iv injection of adiponectin on RSNA and b/p. These findings suggest that adiponectin decreases the RSNA and b/p in a dose-dependent manner and that the SCN is implicated in mechanism of adiponectin actions on RSNA and b/p. These findings also suggest that the hypotensive-action activity of adiponectin is realized, at least partially, via changes in activities of autonomic nerves activity. 相似文献
66.
Chisato Inoue Tomomi Kozaki Yukiko Morita Bungo Shirouchi Katsuya Fukami Kuniyoshi Shimizu Masao Sato Yoshinori Katakura 《Cytotechnology》2015,67(4):721-725
Adipocyte size is closely related to the occurrence of diabetes, metabolic syndrome, and insulin resistance. Thus, researchers are searching for active substances that function to reduce adipocyte size. In the present study, we focused on sugar cane vinegar, Kibizu, and evaluated the function of Kibizu to reduce adipocyte size by using an in vitro model system, because people in Amami Oshima famous for longevity regularly consume Kibizu. Results showed that Kibizu treatment significantly reduced the size and number of lipid droplets in 3T3-L1 cells, relative to treatment with Kurozu, another traditional vinegar. Results of an extraction experiment suggest that the active components in Kibizu are lipophilic and hydrophobic. In addition, an in vivo experiment on rats treated with Kibizu showed that the active components were contained in large vein blood. Results of an additional in vivo experiment suggest that metabolites generated by Kibizu-treated rats are primarily contained or modified specifically in the large vein blood. 相似文献
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69.
Fujii R Minami A Tsukagoshi T Sato N Sahara T Ohgiya S Gomi K Oikawa H 《Bioscience, biotechnology, and biochemistry》2011,75(9):1813-1817
Clustering of biosynthetic genes for producing fungal secondary metabolites, which frequently consist of less than ten genes, has been recognized with numerous genomes. The heterologous expression of whole genes in the clusters will therefore produce various types of natural products when using a suitable fungal host. We introduced the whole gene cluster for the biosynthesis of diterpene aphidicolin into the fungal quadruple auxotrophic host, Aspergillus oryzae, by using four different vectors (pTAex3, pPTRI, pUSA and pAdeA) which harbor a starch-inducible promoter/terminator to examine the expression conditions. The resulting quadruple transformant carrying the genes of geranylgeranyl diphosphate synthase PbGGS, terpene synthase PbACS, and two monooxygenases (PbP450-1 and PbP450-2) produced aphidicolin. The double and triple transformants also respectively produced aphidicolan-16β-ol and 3-deoxyaphidicolin. Alternative host Saccharomyces cerevisiae carrying the genes, PbGGS and PbACS, produced key intermediate aphidicolan-16β-ol. This is the first example of a total biosynthesis of terpenoids using fungal hosts. 相似文献
70.
Nishizawa R Nishiyama T Hisaichi K Minamoto C Murota M Takaoka Y Nakai H Tada H Sagawa K Shibayama S Fukushima D Maeda K Mitsuya H 《Bioorganic & medicinal chemistry》2011,19(13):4028-4042
Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented. 相似文献