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41.
Convergent synthesis and in vivo inhibitory effect on fat accumulation of (-)-ternatin, a highly N-methylated cyclic peptide 总被引:1,自引:0,他引:1
Shimokawa K Yamada K Kita M Uemura D 《Bioorganic & medicinal chemistry letters》2007,17(16):4447-4449
(-)-Ternatin (1), a highly N-methylated cyclic heptapeptide, is a potent inhibitor of fat accumulation against 3T3-L1 murine adipocytes (EC50 = 0.14 microg/mL) [Shimokawa, K.; Mashima, I.; Asai, A.; Yamada, K.; Kita, M.; Uemura, D. Tetrahedron Lett. 2006, 47, 4445]. Compound 1 was synthesized from Boc-protected amino acids in solution. Upon treatment with 1 at 5 mg/kg/day, increases in body weight and fat accumulation in high-fat-fed mice were both significantly suppressed. 相似文献
42.
Zhang X Li C Gao H Nabeka H Shimokawa T Wakisaka H Matsuda S Kobayashi N 《Cellular & molecular biology letters》2011,16(2):279-295
We investigated the effects of Rho-associated kinase (ROCK) on migration and cytoskeletal organization in primary human osteoblasts
and Saos-2 human osteosarcoma cells. Both cell types were exposed to two different ROCK inhibitors, Y-27632 and HA-1077. In
the improved motility assay used in the present study, Y-27632 and HA-1077 significantly increased the migration of both osteoblasts
and osteosarcoma cells on plastic in a dose-dependent and reversible manner. Fluorescent images showed that cells of both
types cultured with Y-27632 or HA-1077 exhibited a stellate appearance, with poor assembly of stress fibers and focal contacts.
Western blotting showed that ROCK inhibitors reduced myosin light chain (MLC) phosphorylation within 5 min without affecting
overall myosin light-chain protein levels. Inhibition of ROCK activity is thought to enhance the migration of human osteoblasts
through reorganization of the actin cytoskeleton and regulation of myosin activity. ROCK inhibitors may be potentially useful
as anabolic agents to enhance the biocompatibility of bone and joint prostheses. 相似文献
43.
Kogure T Shirakawa S Shimokawa M Hosokawa Y 《Journal of physiological anthropology》2011,30(3):103-109
The purpose of this study was to formulate a "sleep/wake" scoring algorithm for processing activity measurements obtained using a newly developed nonwear actigraphy (NWA) device, and to test its validity. The NWA device has a highly sensitive pressure sensor and is placed under a mattress. It can continuously record the activity of a person lying on the mattress and identify an "in-bed/out-of-bed" state from the vibrations of the mattress. We formulated the sleep/wake scoring algorithm by using data obtained simultaneously by wrist actigraphy (Act) and the NWA device in 33 healthy participants. Agreement rate, sensitivity, and specificity with Act were 95.7%, 97.6%, and 75.8% (33 healthy people); the corresponding values were 85.9%, 89.1%, and 79.8% for 12 nursing home residents and 93.7%, 97.2%, and 60.8% for 60 nights for 6 healthy persons who slept 10 nights on their futons. Agreement rate, sensitivity, and specificity with polysomnography were in almost perfect agreement with Act (12 nights; 6 healthy persons who slept 2 nights). All our validation results indicate that the NWA device, placed under a mattress or a futon, can produce almost identical sleep/wake scores to Act. It is expected that the NWA device, a nonwear device for scoring sleep/wake and in-bed/out-of-bed, enables convenient long-term sleep-related evaluation in various fields, including hospital settings, home-care settings, and care facility settings such as nursing homes. 相似文献
44.
The role of wall Ca2+ in the regulation of wall extensibility during the acid-induced extension of soybean hypocotyl cell walls 总被引:1,自引:0,他引:1
We examined the acid-facilitated yielding properties of cell walls of soybean hypocotyls and the effects of Ca(2+) upon the properties by stress-strain analyses using glycerinated hollow cylinders (GHCs) from the elongating regions of the hypocotyls. Stress-extension rate curves of native GHCs showed characteristic changes with pH, all indicating the existence of yield threshold tension (y) as well as wall extensibility (phi), i.e. a downward shift of y and an increase in phi with wall acidification. The acid-induced downward shift of y was inhibited by boiling of GHCs. In contrast, a considerable increase in phi with acidification remained even after boiling. This indicates that phi consists of two components, i.e. heat-sensitive and heat-resistant, both being pH sensitive. A Ca(2+) chelator (Quin 2) dramatically increased phi at a neutral pH. Subsequent addition of Ca(2+) or ruthenium red suppressed the chelator-induced increase in phi. These findings suggest that wall Ca(2+) plays an important role in the regulation of wall extensibility during the acid-induced wall extension by reacting with carboxyl groups of wall pectin. 相似文献
45.
Okada J Shimokawa N Koibuchi N 《The international journal of biochemistry & cell biology》2005,37(7):1368-1374
Polychlorinated biphenyls (PCBs) are known as environmental pollutants that may cause adverse health problems. However, little is known about the effects of PCBs on acid-sensitive neurons of the medulla oblongata, which regulate respiration. Therefore, the present study was designed to examine whether PCB alters acid-sensitivity of cultured neurons derived from the rat medulla oblongata. When extracellular pH was shifted from 7.4 to 7.0, acid-sensitive neurons showed depolarization, which was measured by voltage-sensitive fluorescent dye. Exposure to PCB (Aroclor 1254) decreased the amplitude of depolarization in low pH and increased the resting membrane potential in a dose-dependent manner. Taken together, our results indicate that PCB potentially influences acid-sensitivity through alteration of the membrane potential of acid-sensitive neurons, which could affect the regulation of respiration. 相似文献
46.
47.
Shimokawa Y Akiyama H Kashiyama E Koga T Miyamoto G 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,821(1):8-14
High performance liquid chromatographic (HPLC) methods were validated for the determination of aripiprazole (OPC-14597, Abilify) in rat plasma and brain. Separation was by Nova-pak phenyl column; flow rate, 1.0 ml/min; mobile phase, acetonitrile-methanol-20 mM sodium sulfate-acetic acid (27:25:48:1, v/v/v/v); UV detection at 254 nm. Reproducibility in plasma and brain showed excellent precision (within 7.8 and 10.6%) and accuracy (96.0-102.4% and 99.0-108.7%) with calibration curve ranges 10.0-2000 ng/ml and 30.0-6000 ng/g, respectively. Validated HPLC methods were successfully applied to pharmacokinetic study of aripiprazole in rats, demonstrating brain concentrations after oral administration five times higher than plasma concentrations. 相似文献
48.
49.
Tao Y Nishikawa S Nomura M Kitabatake N Tani F 《Biochemical and biophysical research communications》2005,338(2):700-709
Biotinylated proteins and peptides have been used as popular ligands for characterization of cell surface receptors by a variety of methods including flow cytometry. The number and the location of biotin moieties incorporated could alter the structural and physicochemical properties of ligands, although biotin is thought to be such a small molecule (244Da) that it is capable of being conjugated to most proteins without affecting their activity. Here, we demonstrate that the biotinylated HSP70 molecule via primary amines bound to epithelium-like HEK 293 cells in a saturable manner whereas the unlabeled counterparts of HSP70 other than mouse Hsp72 do not. This binding was not competed by either HSP70 or the biotin entity itself. Interestingly, the biotinylated HSP70 also elicited the production of CC-chemokine RANTES independent of CD40 signaling. This response occurred regardless of sequence diversity of HSP70 derived from different species, and neither the biotinylated ovalbumin nor the unlabeled HSP70 cross-linked with a biotinylated protein stimulated a significant level of RANTES production which was induced by biotinylated HSP70 itself. Our findings suggest that modification of HSP70 such as biotinylation may function as a biological alarm signal in the innate immune system. 相似文献
50.
Here, we produced the C-terminal truncation variants of mouse inducible heat shock protein 72 (Hsp72) to elucidate the regulatory role of the C-terminal helical lid of Hsp70 for substrate recognition. All of the truncation variants containing the substrate binding domain bound a short-length peptide substrate CLLLSAPRR. When a large mass reduced carboxymethyl alpha-lactalbumin (RCMLA) as a substrate was used in gel filtration experiment, we observed the complex formation only for the truncation variants containing the long alpha-helix C in the helical lid. However, RCMLA binding occurred even for the variants lacking alpha-helix C when their C-terminal region was anchored onto a solid phase. Together with the finding that helix C is involved in the self-association of Hsp70, our present data suggest that the C-terminal region of Hsp70 modulates the substrate recognition and its kinetics may be substrate-mass dependent. 相似文献