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21.
Hirotaka Kashiwagi Yoshiyuki Ono Masateru Ohta Susumu Itoh Fumihiko Ichikawa Suguru Harada Satoshi Takeda Nobuo Sekiguchi Masaki Ishigai Tadakatsu Takahashi 《Bioorganic & medicinal chemistry》2013,21(7):1823-1833
In an extension of our study on gamma hydroxy carboxylic acid analogs, we explored a series of nonsecosteroidal vitamin D receptor (VDR) agonists in which 1,3-diol of 1,25(OH)2D3 had been replaced by aryl acetic acid. These analogs showed very potent activity in vitro compared with 1,25(OH)2D3. An X-ray analysis of 8d showed that the inserted phenyl ring well mimicked the folded methylene linker of the gamma hydroxy carboxylic acid moiety but the carboxylic acid of 8d interacted with VDR in a different manner from gamma hydroxy carboxylic acids. Through our in vivo screening in an osteoporosis rat model using immature rats, we identified a potent active vitamin D3 analog, compound 7e. In mature rats of the same model, compound 7e also showed good PK profiling and excellent ability to prevent bone mineral density loss without severe hypercalcemia. Our nonsecosteroidal VDR agonist 7e (CH5036249) could be a possible new drug candidate for treating osteoporosis in human. 相似文献
22.
Ren Matsuba Minako Imamura Yasushi Tanaka Minoru Iwata Hiroshi Hirose Kohei Kaku Hiroshi Maegawa Hirotaka Watada Kazuyuki Tobe Atsunori Kashiwagi Ryuzo Kawamori Shiro Maeda 《PloS one》2016,11(4)
AimWe performed a replication study in a Japanese population to evaluate the association between type 2 diabetes and six susceptibility loci (TMEM154, SSR1, FAF1, POU5F1, ARL15, and MPHOSPH9) originally identified by a transethnic meta-analysis of genome-wide association studies (GWAS) in 2014.MethodsWe genotyped 7,620 Japanese participants (5,817 type 2 diabetes patients and 1,803 controls) for each of the single nucleotide polymorphisms (SNPs) using a multiplex polymerase chain reaction invader assay. The association of each SNP locus with the disease was evaluated using logistic regression analysis.ResultsOf the six SNPs examined in this study, four (rs6813195 near TMEM154, rs17106184 in FAF1, rs3130501 in POU5F1 and rs4275659 near MPHOSPH9) had the same direction of effect as in the original reports, but two (rs9505118 in SSR1 and rs702634 in ARL15) had the opposite direction of effect. Among these loci, rs3130501 and rs4275659 were nominally associated with type 2 diabetes (rs3130501; p = 0.017, odds ratio [OR] = 1.113, 95% confidence interval [CI] 1.019–1.215, rs4275659; p = 0.012, OR = 1.127, 95% CI 1.026–1.238, adjusted for sex, age and body mass index), but we did not observe a significant association with type 2 diabetes for any of the six evaluated SNP loci in our Japanese population.ConclusionsOur results indicate that effects of the six SNP loci identified in the transethnic GWAS meta-analysis are not major among the Japanese, although SNPs in POU5F1 and MPHOSPH9 loci may have some effect on susceptibility to type 2 diabetes in this population. 相似文献
23.
Murakami Shinsuke Nakatani Jun Nakajima Kenichi Amasawa Eri Ii Ryota Hayashi Kiyotada Yoshikawa Naoki Daigo Ichiro Kishita Yusuke Ihara Tomohiko Shobatake Koichi Kudoh Yuki Motoshita Masaharu Kanemoto Keiichiro Hara Minako Kashiwagi Aiichiro Hashimoto Seiji Shigetomi Yosuke Kanzaki Masayuki Kikuchi Yasunori Ohno Hajime Fukushima Yasuhiro 《The International Journal of Life Cycle Assessment》2019,24(8):1544-1552
The International Journal of Life Cycle Assessment - 相似文献
24.
Takemoto T Nishio Y Sekine O Ikeuchi C Nagai Y Maeno Y Maegawa H Kimura H Kashiwagi A 《FEBS letters》2007,581(2):218-222
In rodents a high-fructose diet induces metabolic derangements similar to those in metabolic syndrome. Previously we suggested that in mouse liver an unidentified nuclear protein binding to the sterol regulatory element (SRE)-binding protein-1c (SREBP-1c) promoter region plays a key role for the response to high-fructose diet. Here, using MALDI-TOF MASS technique, we identified an X-chromosome-linked RNA binding motif protein (RBMX) as a new candidate molecule. In electrophoretic mobility shift assay, anti-RBMX antibody displaced the bands induced by fructose-feeding. Overexpression or suppression of RBMX on rat hepatoma cells regulated the SREBP-1c promoter activity. RBMX may control SREBP-1c expression in mouse liver in response to high-fructose diet. 相似文献
25.
Morita Y Araki H Sugimoto T Takeuchi K Yamane T Maeda T Yamamoto Y Nishi K Asano M Shirahama-Noda K Nishimura M Uzu T Hara-Nishimura I Koya D Kashiwagi A Ohkubo I 《FEBS letters》2007,581(7):1417-1424
Legumain/asparaginyl endopeptidase (EC 3.4.22.34) is a novel cysteine protease that is abundantly expressed in the late endosomes and lysosomes of renal proximal tubular cells. Recently, emerging evidence has indicated that legumain might play an important role in control of extracellular matrix turnover in various pathological conditions such as tumor growth/metastasis and progression of atherosclerosis. We initially found that purified legumain can directly degrade fibronectin, one of the main components of the extracellular matrix, in vitro. Therefore, we examined the effect of legumain on fibronectin degradation in cultured mouse renal proximal tubular cells. Fibronectin processing can be inhibited by chloroquine, an inhibitor of lysosomal degradation, and can be enhanced by the overexpression of legumain, indicating that fibronectin degradation occurs in the presence of legumain in lysosomes from renal proximal tubular cells. Furthermore, in legumain-deficient mice, unilateral ureteral obstruction (UUO)-induced renal interstitial protein accumulation of fibronectin and renal interstitial fibrosis were markedly enhanced. These findings indicate that legumain might have an important role in extracellular matrix remodeling via the degradation of fibronectin in renal proximal tubular cells. 相似文献
26.
Sugiura T Horiguchi H Sugahara K Takeda C Samejima M Fujii A Okita Y 《Journal of physiological anthropology》2007,26(2):257-259
Preliminary experiments were carried out to investigate the feasibility of using an electroencephalogram and heart rates to evaluate the efficacy of finger acupressure on the key points of planta pedis (both soles). Continuous electroencephalograms were recorded from 19 electrodes based on the International 10-20 electrode placement system on 22 university students (21+/-2.3 years). Spectral power changes were obtained at each electrode site. The power of the alpha1 frequency range (8-10 Hz) increased slightly during acupressure although no statistical significance was observed, while heart rates decreased in all subjects (p<0.05). Cerebral cortex asymmetry in the spectral power changes was not clearly observed during the right and left sole acupressure. This preliminary study suggests that a classification of subjects is necessary in understanding brain wave data during acupressure on soles. 相似文献
27.
Yoshida M Kashiwagi K Kawai G Ishihama A Igarashi K 《The Journal of biological chemistry》2001,276(19):16289-16295
The effects of polyamines on the synthesis of various final sigma subunits of RNA polymerase were studied using Western blot analysis. Synthesis of final sigma(28) was stimulated 4.0-fold and that of final sigma(38) was stimulated 2.3-fold by polyamines, whereas synthesis of other final sigma subunits was not influenced by polyamines. Stimulation of final sigma(28) synthesis was due to an increase in the level of cAMP, which occurred through polyamine stimulation of the synthesis of adenylate cyclase at the level of translation. Polyamines were found to increase the translation of adenylate cyclase mRNA by facilitating the UUG codon-dependent initiation. Analysis of RNA secondary structure suggests that exposure of the Shine-Dalgarno sequence of mRNA is a prerequisite for polyamine stimulation of the UUG codon-dependent initiation. 相似文献
28.
Sharmin S Sakata K Kashiwagi K Ueda S Iwasaki S Shirahata A Igarashi K 《Biochemical and biophysical research communications》2001,282(1):228-235
The toxicity of extracellular spermine, determined in the presence of fetal calf serum, was studied using three cell lines: FM3A, L1210, and NIH3T3 cells. Amine oxidase in fetal calf serum produces aminodialdehyde generating acrolein spontaneously, H(2)O(2), and ammonia from spermine. Spermine toxicity was prevented by aldehyde dehydrogenase, but not by catalase. Similar concentrations of spermine and acrolein were needed to produce toxicity. Other aldehydes (formaldehyde, acetaldehyde, and propionaldehyde) and hydrogen peroxide were less toxic than acrolein. Spermidine and 3-aminopropanal, which produces acrolein, also exhibited severe cytotoxicity. The degree of cytotoxicity of spermine, spermidine, and 3-aminopropanal was nearly parallel with the amount of acrolein produced from each compound. Thus, it was deduced that acrolein is a major toxic compound produced from polyamines (spermine and spermidine) by amine oxidase. 相似文献
29.
Kashiwagi K Fukami-Kobayashi K Shiba K Nishikawa K 《Bioscience, biotechnology, and biochemistry》2004,68(4):808-813
The respective type-1 and type-2 periplasmic binding proteins (PBPs) MglB and ArgT are believed to have evolved from a common ancestor into siblings showing topological differences in their main chain connectivity. At first glance, they show similar structure. But, more detailed examination reveals that the chain connectivity of ArgT is more convoluted than that of MglB. Reflecting that complexity, the folding of ArgT is complicated and involves intermediate folds. On the other hand, the folding of MglB is a simple two-state transition. In the present study, we constructed and characterized several chimeras made up of various subdomains of MglB and ArgT with the aim of gaining insight into the evolution of protein folding and protein structure. Although these chimeras did not fold as compactly as their parental proteins, some did exhibit cooperative folding, which suggests that novel proteins with new connectivity and new folding pathways could have emerged at a fairly high rate throughout the evolution of proteins. 相似文献
30.
Kamiya A Michikami D Shiozawa T Iwase S Hayano J Kawada T Sunagawa K Mano T 《American journal of physiology. Regulatory, integrative and comparative physiology》2004,286(5):R844-R850
Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6 degrees head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by approximately 70% at both exercise intensities (both P < 0.05 vs. before bed rest) and reduced the maximal voluntary force of plantar flexion by 15%. In contrast, bed rest did not alter the increase in MSNA response to fatiguing handgrip and had no effects on the maximal voluntary force of handgrip. Although PEMI sustained MSNA activation before bed rest in all trials, bed rest entirely eliminated the PEMI-induced increase in MSNA in leg exercises but partially attenuated it in forearm exercises. These results do not support our hypothesis but indicate that bed rest causes a reduction in isometric exercise-induced sympathetic activation in (probably atrophied) antigravity leg muscles. 相似文献