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921.
Yan Dong Miku Hirane Mutsumi Araki Nobuyuki Fukushima Toshifumi Tsujiuchi 《Biochemical and biophysical research communications》2014
Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors (LPA1–LPA6) mediates a variety of biological functions, including cell migration. Recently, we have reported that LPA1 inhibited the cell motile activities of mouse fibroblast 3T3 cells. In the present study, to evaluate a role of LPA5 in cellular responses, Lpar5 knockdown (3T3-L5) cells were generated from 3T3 cells. In cell proliferation assays, LPA markedly stimulated the cell proliferation activities of 3T3-L5 cells, compared with control cells. In cell motility assays with Cell Culture Inserts, the cell motile activities of 3T3-L5 cells were significantly higher than those of control cells. The activity levels of matrix metalloproteinases (MMPs) were measured by gelatin zymography. 3T3-L5 cells stimulated the activation of Mmp-2, correlating with the expression levels of Mmp-2 gene. Moreover, to assess the co-effects of LPA1 and LPA5 on cell motile activities, Lpar5 knockdown (3T3a1-L5) cells were also established from Lpar1 over-expressing (3T3a1) cells. 3T3a1-L5 cells increased the cell motile activities of 3T3a1 cells, while the cell motile activities of 3T3a1 cells were significantly lower than those of control cells. These results suggest that LPA5 may act as a negative regulator of cellular responses in mouse fibroblast 3T3 cells, similar to the case for LPA1. 相似文献
922.
Masayuki Sakiyama Hirotaka Matsuo Seiko Shimizu Toshinori Chiba Akiyoshi Nakayama Yuzo Takada Takahiro Nakamura Tappei Takada Emi Morita Mariko Naito Kenji Wakai Hiroki Inoue Seishiro Tatsukawa Junki Sato Kazumi Shimono Toshiaki Makino Takahiro Satoh Hiroshi Suzuki Yoshikatsu Kanai Nobuyuki Hamajima Yutaka Sakurai Kimiyoshi Ichida Toru Shimizu Nariyoshi Shinomiya 《Human cell》2014,27(1):1-4
Gout is a common disease resulting from hyperuricemia which causes acute arthritis. Recently, genome-wide association studies revealed an association between serum uric acid levels and a common variant of leucine-rich repeat-containing 16A (LRRC16A) gene. However, it remains to be clarified whether LRRC16A contributes to the susceptibility to gout. In this study, we investigated the relationship between rs742132 in LRRC16A and gout. A total of 545 Japanese male gout cases and 1,115 male individuals as a control group were genotyped. rs742132 A/A genotype significantly increased the risk of gout, conferring an odds ratio of 1.30 (95 % CI 1.05–1.60; p = 0.015). LRRC16A encodes a protein called capping protein ARP2/3 and myosin-I linker (CARMIL), which serves as an inhibitor of the actin capping protein (CP). CP is an essential element of the actin cytoskeleton, which binds to the barbed end of the actin filament and regulates its polymerization. In the apical membrane of proximal tubular cells in the human kidney, the urate-transporting multimolecular complex (urate transportsome) is proposed to consist of several urate transporters and scaffolding proteins, which interact with the actin cytoskeleton. Thus, if there is a CARMIL dysfunction and regulatory disability in actin polymerization, urate transportsome may be unable to operate appropriately. We have shown for the first time that CARMIL/LRRC16A was associated with gout, which could be due to urate transportsome failure. 相似文献
923.
Yukio Agatsuma Hikaru Endo Shigeki Yoshida Chikara Ikemori Yoshio Takeuchi Hiroaki Fujishima Kazuhiko Nakajima Mitsuhiro Sano Nobuyuki Kanezaki Hisaeki Imai Naoki Yamamoto Hiroki Kanahama Takashi Matsubara Satoshi Takahashi Tatsuhiko Isogai Kazuya Taniguchi 《Journal of applied phycology》2014,26(4):1845-1852
Apart from certain studies on Macrocystis pyrifera (Linnaeus) C. Agardh, very few in situ experimental studies on production have been carried out to verify that “bottom–up effects” (relating to nutrient supply) are more important than “top–down” effects (relating to herbivory) in temperate kelp forests. The effects of nutrient supply on recruitment and production of hatchery-raised gametophytes of Saccharina japonica, cultivated on a rope, and wild Saccharina religiosa, cultivated on a rope and on new concrete reefs placed at the sea bottom, were examined at an experimental site with artificial nutrient addition continuously from October 2008 to May 2009 and compared to kelp that was cultivated from October 2008 to May 2009 without nutrient supply, at a natural site in Tomari (Sea of Japan, southwestern Hokkaido, Japan). At both sites, sea urchins were removed for exclusion of top–down effect. At the natural site, no hatchery-raised S. japonica and wild S. religiosa grew on the rope. No wild S. religiosa grew on the porous-concrete reefs and rocks. At the nutrient-enhanced site, S. japonica and S. religiosa grew rapidly on the rope, at rates of 47.7 and 33.3 plants/10 cm length rope, respectively. S. religiosa grew on the concrete reefs at a concentration of 9.7 plants/0.3 m2. At the nutrient-enhanced site, the concentrations of NH4-N, NO3-N, NO2-N, and PO4-P ranged from 35.2–173.2, 2.1–10.9, 0.3–1.5, and 0.8–2.6 μmol L?1, respectively, being markedly higher than those at the natural site, where these nutrient concentrations were almost equal to the averages off Tomari. These results indicate that the production of Saccharina kelp is restricted by bottom–up effects (at a low nutrient concentration) in the Sea of Japan, southwestern Hokkaido. Nutrient supply would be essential for growth enhancement of Saccharina kelp production in a marine environment around Japan where, in recent times, water temperatures have increased by ca. 0.5 °C and nutrient concentrations have decreased. 相似文献
924.
925.
926.
Nobuyuki Horita Naoki Miyazawa Ryota Kojima Miyo Inoue Yoshiaki Ishigatsubo Atsuhisa Ueda Takeshi Kaneko 《Respiratory research》2014,15(1):80
Background
Recent observational studies have suggested that use of statins reduces mortality in patients suffering from chronic obstructive pulmonary disease. However, no meta-analysis has reported the pooled hazard ratio of statins to all-cause mortality.Methods
We searched for eligible articles using five databases. We included randomized controlled trials and cohort studies written in English using original data reporting the hazard ratio of statins to all-cause, cardiovascular-related, cancer-related, or respiratory-related mortality. A fixed model with the confidence interval method was used. Publication bias was evaluated by funnel plot and Begg’s test, and was corrected using Duval’s trim and fill method. Sensitivity analyses were also conducted.Results
We included 10 out of 128 articles. The pooled hazard ratio of statins to all-cause mortality involving 16269 patients was 0.81 (95% CI: 0.75-0.86, P < 0.001) with moderate heterogeneity (I2 = 52%, P = 0.032). The sensitivity analysis and funnel plot suggested the existence of publication bias. After three possibly unpublished cohorts were imputed, the pooled hazard ratio of 0.83 (95% CI: 0.78-0.88, P < 0.001) still suggested a favorable prognosis in statin-treated patients. The pooled hazard ratio of statins to cardiovascular-related, cancer-related, and respiratory-related mortality were 0.52 (95% CI: 0.27-1.01, P = 0.052), 0.57 (95% CI: 0.32-1.01, P = 0.056), and 0.55 (95% CI: 0.43-0.78, P < 0.001), respectively, although these results were not conclusive as we could not find a sufficient number of original studies dealing with those forms of mortality.Conclusions
The use of statins for patients suffering from chronic obstructive pulmonary disease may reduce all-cause mortality. This conclusion should be re-evaluated by a registered large-scale randomized controlled trial. 相似文献927.
928.
Takanori Yamada Mami Furukawa Ayako Yamasaki Nobuyuki Fukushima 《Biochemical and biophysical research communications》2009,378(3):424-793
Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell proliferation, migration, and protects cells from apoptosis. It interacts with specific G protein-coupled transmembrane receptors. In this study, mutations of lysophosphatidic acid receptor-1 (LPA1) gene were investigated to clarify the possible molecular mechanisms underlying the development of lung tumors induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Male Wistar rats, 6 weeks of age, were given 2000 ppm BHP in their drinking water for 12 weeks and then maintained without further treatment until sacrifice at 25 weeks. Genomic DNAs were extracted from paraffin-embedded tissues and exons 2-4 were examined for mutations, using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. No LPA1 mutations were detected in 15 hyperplasias, but 2 out of 12 adenomas (16.7%) and 7 out of 17 adenocarcinomas (41.2%). These results suggest that mutations of LPA1 gene may be involved in the acquisition of growth advantage from adenomas to adenocarcinomas in lung carcinogenesis induced in rats by BHP. 相似文献
929.
Nobuyuki Takei Mihoko Kawamura Yuta Ishizuka Naomasa Kakiya Naoko Inamura Hisaaki Namba Hiroyuki Nawa 《The Journal of biological chemistry》2009,284(39):26340-26348
The constitutive and activity-dependent components of protein synthesis are both critical for neural function. Although the mechanisms controlling extracellularly induced protein synthesis are becoming clear, less is understood about the molecular networks that regulate the basal translation rate. Here we describe the effects of chronic treatment with various neurotrophic factors and cytokines on the basal rate of protein synthesis in primary cortical neurons. Among the examined factors, brain-derived neurotrophic factor (BDNF) showed the strongest effect. The rate of protein synthesis increased in the cortical tissues of BDNF transgenic mice, whereas it decreased in BDNF knock-out mice. BDNF specifically increased the level of the active, unphosphorylated form of eukaryotic elongation factor 2 (eEF2). The levels of active eEF2 increased and decreased in BDNF transgenic and BDNF knock-out mice, respectively. BDNF decreased kinase activity and increased phosphatase activity against eEF2 in vitro. Additionally, BDNF shortened the ribosomal transit time, an index of translation elongation. In agreement with these results, overexpression of eEF2 enhanced protein synthesis. Taken together, our results demonstrate that the increased level of active eEF2 induced by chronic BDNF stimulation enhances translational elongation processes and increases the total rate of protein synthesis in neurons.The synthesis and post-translational modification of proteins play key roles in neural development, synaptic plasticity, and cognitive brain functions such as learning and memory (1, 2). Recent studies have revealed that activity-dependent regulation of translation affects neural plasticity (3, 4). Previously, we reported that BDNF,2 a critical molecule for neural plasticity (5–7), enhances protein synthesis and activates the translational machinery in central nervous system neurons (8). In addition, neurotransmitters such as glutamate (9, 10), dopamine (11), and serotonin (12) are also reported to facilitate translation in neurons. These observations indicate that endogenous molecules can acutely modulate neuronal translation in response to neural activity. Translation of an mRNA molecule comprises three steps: initiation, elongation, and release (or termination) (13). In the first step, mRNA and methionyl-tRNAiMet are recruited to a ribosome. During elongation, aminoacyl-tRNAs are sequentially recruited and the nascent peptide chain lengthens incrementally as amino acids are covalently attached via peptide bonds. Finally, the polypeptide chain is released from the ribosome. Each step is regulated by a variety of factors. The activities of these regulatory proteins are predominantly controlled by phosphorylation and GTP binding. BDNF activates both initiation and elongation by modulating these processes (8, 14, 15).In addition to these acute, stimulation-induced changes in the translation rate, the long term regulation of translation plays important roles in developing and mature brains. In fact, recent studies have shown that genetic disruption or overexpression of translation factors or modulator genes alters synaptic plasticity and behavior as well as the basal rate of protein synthesis. Mice lacking the gene encoding GCN2, a kinase that phosphorylates eIF2α, exhibited enhanced translation as well as aberrant long term potentiation and spatial learning (16). Similar phenotypes have been observed in mice carrying a constitutively active mutant variant (Ser52 to Ala) of eIF2α (17). Mice lacking eIF4E-binding protein 2 (4EBP2) exhibited increased cap-dependent translation and altered long-term potentiation, long-term depression (LTD), and learning (18, 19). Mice expressing a transgene encoding a dominant-negative version of MEK, which inhibits the phosphorylation of eIF4E and protein synthesis, were found to have learning deficits (20). Thus, modifying the rate of protein synthesis can produce deleterious effects on synaptic plasticity and brain function.Although genetic modifications can affect translation, the mechanisms by which the basal translation rate is controlled in normal neurons are unknown. Here, we demonstrate that chronic treatment of primary cortical neurons with BDNF increases the level of active, unphosphorylated eukaryotic elongation factor 2 (eEF2) and enhances the rates of elongation and protein synthesis. Analysis of BDNF mutant mice supports a role for this neurotrophin in regulating the basal rate of protein synthesis. 相似文献
930.
Nadia Corp Hitoshige Hayaki Takahisa Matsusaka Shiho Fujita Kazuhiko Hosaka Nobuyuki Kutsukake Michio Nakamura Miho Nakamura Hitonaru Nishie Masaki Shimada Koichiro Zamma William Wallauer Toshisada Nishida 《Primates; journal of primatology》2009,50(2):184-189
In 1998, four chimpanzees in the Mahale Mountains National Park, Tanzania, were observed wiping their mouths with non-detached
leaves or stalks of grass, or rubbing their mouths with a tree trunk or branch, especially while eating lemons. The number
of mouth-wiping/rubbing individuals increased to 18 in 1999. By 2005, 29 chimpanzees were documented wiping/rubbing their
muzzles in this way. Although it is difficult to determine whether the chimpanzees acquired this behavior as a result of trial
and error or social learning, the fact that chimpanzees at other sites perform this behavior with detached leaves or leafy
twigs much more often than with intact items suggests the possibility that cleaning with intact plant parts at Mahale spread
via social learning. 相似文献