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81.
Ishikawa S Kuno A Tanno M Miki T Kouzu H Itoh T Sato T Sunaga D Murase H Miura T 《American journal of physiology. Heart and circulatory physiology》2012,302(12):H2536-H2544
Sarcolemmal connexin-43 (Cx43) and mitochondrial Cx43 play distinct roles: formation of gap junctions and production of reactive oxygen species (ROS) for redox signaling. In this study, we examined the hypothesis that Cx43 contributes to activation of a major cytoprotective signal pathway, phosphoinositide 3-kinase (PI3K)-Akt-glycogen synthase kinase-3β (GSK-3β) signaling, in cardiomyocytes. A δ-opioid receptor agonist {[d-Ala(2),d-Leu(5)]enkephalin acetate (DADLE)}, endothelin-1 (ET-1), and insulin-like growth factor-1 (IGF-1) induced phosphorylation of Akt and GSK-3β in H9c2 cardiomyocytes. Reduction of Cx43 protein to 20% of the normal level by Cx43 small interfering RNA abolished phosphorylation of Akt and GSK-3β induced by DADLE or ET-1 but not that induced by IGF-1. DADLE and IGF-1 protected H9c2 cells from necrosis after treatment with H(2)O(2) or antimycin A. The protection by DADLE or ET-1, but not that by IGF-1, was lost by reduction of Cx43 protein expression. In contrast to Akt and GSK-3β, PKC-ε, ERK and p38 mitogen-activated protein kinase were phosphorylated by ET-1 in Cx43-knocked-down cells. Like diazoxide, an activator of the mitochondrial ATP-sensitive K(+) channel, DADLE and ET-1 induced significant ROS production in mitochondria, although such an effect was not observed for IGF-1. Cx43 knockdown did not attenuate the mitochondrial ROS production by DADLE or ET-1. Cx43 was coimmunoprecipitated with the β-subunit of G protein (Gβ), and knockdown of Gβ mimicked the effect of Cx43 knockdown on ET-1-induced phosphorylation of Akt and GSK-3β. These results suggest that Cx43 contributes to activation of class I(B) PI3K in PI3K-Akt-GSK-3β signaling possibly as a cofactor of Gβ in cardiomyocytes. 相似文献
82.
83.
Ryunosuke Yoshino Nobuaki Yasuo Daniel Ken Inaoka Yohsuke Hagiwara Kazuki Ohno Masaya Orita Masayuki Inoue Tomoo Shiba Shigeharu Harada Teruki Honma Emmanuel Oluwadare Balogun Josmar Rodrigues da Rocha Carlos Alberto Montanari Kiyoshi Kita Masakazu Sekijima 《PloS one》2015,10(5)
BackgroundChagas disease, caused by the parasite Trypanosoma cruzi, is a neglected tropical disease that causes severe human health problems. To develop a new chemotherapeutic agent for the treatment of Chagas disease, we predicted a pharmacophore model for T. cruzi dihydroorotate dehydrogenase (TcDHODH) by fragment molecular orbital (FMO) calculation for orotate, oxonate, and 43 orotate derivatives.Conclusions/SignificanceFMO-based interaction energy analyses revealed a pharmacophore model for TcDHODH inhibitor. Hydrogen bond acceptor pharmacophores correspond to Lys43 and Lys214, hydrogen bond donor and acceptor pharmacophores correspond to Asn67 and Asn194, and the aromatic ring pharmacophore corresponds to FMN, which shows important characteristics of compounds that inhibit TcDHODH. In addition, the Lys214 residue is not conserved between TcDHODH and human DHODH. Our analysis suggests that these orotate derivatives should preferentially bind to TcDHODH, increasing their selectivity. Our results obtained by pharmacophore modeling provides insight into the structural requirements for the design of TcDHODH inhibitors and their development as new anti-Chagas drugs. 相似文献
84.
Masaya Ito Kate H. Bentley Yuki Oe Shun Nakajima Hiroko Fujisato Noriko Kato Mitsuhiro Miyamae Ayako Kanie Masaru Horikoshi David H. Barlow 《PloS one》2015,10(4)
Background
The Overall Depression Severity and Impairment Scale (ODSIS) is a brief, five-item measure for assessing the frequency and intensity of depressive symptoms, as well as functional impairments in pleasurable activities, work or school, and interpersonal relationships due to depression. Although this scale is expected to be useful in various psychiatric and mental health settings, the reliability, validity, and interpretability have not yet been fully examined. This study was designed to examine the reliability, factorial, convergent, and discriminant validity of a Japanese version of the ODSIS, as well as its ability to distinguish between individuals with and without a major depressive disorder diagnosis.Methods
From a pool of registrants at an internet survey company, 2830 non-clinical and clinical participants were selected randomly (619 with major depressive disorder, 619 with panic disorder, 576 with social anxiety disorder, 645 with obsessive–compulsive disorder, and 371 non-clinical panelists). Participants were asked to respond to the ODSIS and conventional measures of depression, functional impairment, anxiety, neuroticism, satisfaction with life, and emotion regulation.Results
Exploratory and confirmatory factor analysis of three split subsamples indicated the unidimensional factor structure of ODSIS. Multi-group confirmatory factor analysis showed invariance of factor loadings between non-clinical and clinical subsamples. The ODSIS also showed excellent internal consistency and test–retest intraclass correlation coefficients. Convergence and discriminance of the ODSIS with various measures were in line with our expectations. Receiver operating characteristic curve analyses showed that the ODSIS was able to detect a major depressive syndrome accurately.Conclusions
This study supports the reliability and validity of ODSIS in a non-western population, which can be interpreted as demonstrating cross-cultural validity. 相似文献85.
Masaya Ikezaki Mikiko Kojima Hitoshi Sakakibara Shoko Kojima Yoshihisa Ueno Chiyoko Machida Yasunori Machida 《The Plant journal : for cell and molecular biology》2010,61(1):70-82
The asymmetric leaves 1 ( as1 ) and as2 mutants of Arabidopsis thaliana exhibit pleiotropic phenotypes. Expression of a number of genes, including three class-1 KNOTTED -like homeobox ( KNOX ) genes ( BP , KNAT2 and KNAT6 ) and ETTIN / ARF3 , is enhanced in these mutants. In the present study, we attempted to identify the phenotypic features of as1 and as2 mutants that were generated by ectopic expression of KNOX genes, using multiple loss-of-function mutations of KNOX genes as well as as1 and as2 . Our results revealed that the ectopic expression of class-1 KNOX genes resulted in reductions in the sizes of leaves, reductions in the size of sepals and petals, the formation of a less prominent midvein, the repression of adventitious root formation and late flowering. Our results also revealed that the reduction in leaf size and late flowering were caused by the repression, by KNOX genes, of a gibberellin (GA) pathway in as1 and as2 plants. The formation of a less prominent midvein and the repression of adventitious root formation were not, however, related to the GA pathway. The asymmetric formation of leaf lobes, the lower complexity of higher-ordered veins, and the elevated frequency of adventitious shoot formation on leaves of as1 and as2 plants were not rescued by multiple mutations in KNOX genes. These features must, therefore, be controlled by other genes in which expression is enhanced in the as1 and as2 mutants. 相似文献
86.
Masaya Yamamoto 《Biochemical and biophysical research communications》2010,393(3):384-389
Misfolded proteins produced in the endoplasmic reticulum (ER) are degraded by a mechanism, the ER-associated degradation (ERAD). Here we report establishment of the experimental system to analyze the ERAD in plant cells. Carboxypeptidase Y (CPY) is a vacuolar enzyme and its mutant CPY∗ is degraded by the ERAD in yeast. Since Arabidopsis thaliana has AtCPY, an ortholog of yeast CPY, we constructed and expressed fusion proteins consisting of AtCPY and GFP and of AtCPY∗, which carries a mutation homologous to yeast CPY∗, and GFP in A. thaliana cells. While AtCPY-GFP was efficiently transported to the vacuole, AtCPY∗-GFP was retained in the ER to be degraded in proteasome- and Cdc48-dependent manners. We also found that AtCPY∗-GFP was degraded by the ERAD in yeast cells, but that its single N-glycan did not function as a degradation signal in yeast or plant cells. Therefore, AtCPY∗-GFP can be used as a marker protein to analyze the ERAD pathway, likely for nonglycosylated substrates, in plant cells. 相似文献
87.
Nobuo Okahashi Masanobu Nakata Yutaka Terao Masaya Yamaguchi Tomoko Sumitomo Shigetada Kawabata 《Biochemical and biophysical research communications》2010,391(2):1192-37577
Streptococcus sanguinis is a predominant bacterium in the human oral cavity and occasionally causes infective endocarditis. We identified a unique cell surface polymeric structure named pili in this species and investigated its functions in regard to its potential virulence. Pili of S. sanguinis strain SK36 were shown to be composed of three distinctive pilus proteins (PilA, PilB, and PilC), and a pili-deficient mutant demonstrated reduced bacterial adherence to HeLa and human oral epithelial cells. PilC showed a binding ability to fibronectin, suggesting that pili are involved in colonization by this species. In addition, ATCC10556, a standard S. sanguinis strain, was unable to produce pili due to defective pilus genes, which indicates a diversity of pilus expression among various S. sanguinis strains. 相似文献
88.
Junichi Matsubara Masaya Ono Kazufumi Honda Ayako Negishi Hideki Ueno Takuji Okusaka Junji Furuse Koh Furuta Emiko Sugiyama Yoshiro Saito Nahoko Kaniwa Junichi Sawada Ayako Shoji Tomohiro Sakuma Tsutomu Chiba Nagahiro Saijo Setsuo Hirohashi Tesshi Yamada 《Molecular & cellular proteomics : MCP》2010,9(4):695-704
89.
The carbon-source dependency of the sexual process in Schizosaccharomycesjaponicus was studied. Schiz. japonicus grew well in vegetativemedia containing glucose, sucrose, fructose or raffinose, anddid poorly in one containing mannose. On the other hand, itssexual process proceeded well in sporulation media containingglucose, sucrose or mannose, and was markedly delayed in thosecontaining fructose or raffinose. Neither vegetative growthnor sexual process occurred when non-fermentable carbon sources,such as glycerol, were used. The amount of glucose in the sporulationmedium sufficient for completion of the sexual process varieddepending on the cell-population density. Glucose was requiredfor both zygote and ascus formation but not for spore liberation.Cells were committed to sporulation shortly after the stageof zygote formation. (Received August 3, 1978; ) 相似文献
90.