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991.
Keisuke Okada Hideaki Miyake Kohei Yamaguchi Koji Chiba Kazuhiro Maeta Shymaa E. Bilasy Hironori Edamatsu Tohru Kataoka Masato Fujisawa 《Biochemical and biophysical research communications》2014
Small GTPase Rap1 has been implicated in the proper differentiation of testicular germ cells. In the present study, we investigated the functional significance of RA-GEF-2/Rapgef6, a guanine nucleotide exchange factor for Rap1, in testicular differentiation using mice lacking RA-GEF-2. RA-GEF-2 was expressed predominantly on the luminal side of the seminiferous tubules in wild-type mice. No significant differences were observed in the body weights or hormonal parameters of RA-GEF-2−/− and wild-type mice. However, the testes of RA-GEF-2−/− male mice were significantly smaller than those of wild-type mice and were markedly atrophied as well as hypospermatogenic. The concentration and motility of epididymal sperm were also markedly reduced and frequently had an abnormal shape. The pregnancy rate and number of fetuses were markedly lower in wild-type females after they mated with RA-GEF-2−/− males than with wild-type males, which demonstrated the male infertility phenotype of RA-GEF-2−/− mice. Furthermore, a significant reduction and alteration were observed in the expression level and cell junctional localization of N-cadherin, respectively, in RA-GEF-2−/− testes, which may, at least in part, account for the defects in testicular differentiation and spermatogenesis in these mice. 相似文献
992.
Yuichiro Enoki Tsuyoshi Sato Shinya Tanaka Takanori Iwata Michihiko Usui Shu Takeda Shoichiro Kokabu Masahito Matsumoto Masahiko Okubo Keisuke Nakashima Masayuki Yamato Teruo Okano Toru Fukuda Dai Chida Yuuki Imai Hisataka Yasuda Tatsuji Nishihara Masumi Akita Hiromi Oda Yasushi Okazaki Tatsuo Suda Tetsuya Yoda 《FEBS letters》2014
Bone is a highly vascularized organ, thus angiogenesis is a vital process during bone remodeling. However, the role of vascular systems in bone remodeling is not well recognized. Here we show that netrin-4 inhibits osteoclast differentiation in vitro and in vivo. Co-cultures of bone marrow macrophages with vascular endothelial cells markedly inhibited osteoclast differentiation. Adding a neutralizing antibody, or RNA interference against netrin-4, restored in vitro osteoclast differentiation. Administration of netrin-4 prevented bone loss in an osteoporosis mouse model by decreasing the osteoclast number. We propose that vascular endothelial cells interact with bone in suppressing bone through netrin-4. 相似文献
993.
In Saccharomyces cerevisiae, under nitrogen-starvation conditions, the α-mannosidase Ams1 is recognized by the autophagic receptor Atg34 and transported into the vacuole, where it functions as an active enzyme. In this study, we identified Hrr25 as the kinase that phosphorylates Atg34 under these conditions. Hrr25-mediated phosphorylation does not affect the interaction of Atg34 with Ams1, but instead promotes Atg34 binding to the adaptor protein Atg11, which recruits the autophagy machinery to the Ams1–Atg34 complex, resulting in activation of the vacuolar transport of Ams1. Our findings reveal the regulatory mechanism of a biosynthetic pathway mediated by the autophagy machinery. 相似文献
994.
Sakae Maeda Hiroshi Wada Yoko Naito Hiroaki Nagano Szandor Simmons Yoshinori Kagawa Atsushi Naito Junichi Kikuta Taeko Ishii Yoshito Tomimaru Naoki Hama Koichi Kawamoto Shogo Kobayashi Hidetoshi Eguchi Koji Umeshita Hideshi Ishii Yuichiro Doki Masaki Mori Masaru Ishii 《The Journal of biological chemistry》2014,289(34):23786-23795
Interferon-α (IFN-α) is used clinically to treat hepatocellular carcinoma (HCC), although the detailed therapeutic mechanisms remain elusive. In particular, IFN-α has long been implicated in control of the cell cycle, but its actual point of action has not been clarified. Here, using time lapse imaging analyses of the human HCC cell line HuH7 carrying a fluorescence ubiquitination-based cell cycle indicator (Fucci), we found that IFN-α induced cell cycle arrest in the G0/G1 phases, leading to apoptosis through an IFN-α type-2 receptor (IFNAR2)-dependent signaling pathway. Detailed analyses by time lapse imaging and biochemical assays demonstrated that the IFN-α/IFNAR2 axis sensitizes cells to apoptosis in the S/G2/M phases in preparation for cell death in the G0/G1 phases. In summary, this study is the first to demonstrate the detailed mechanism of IFN-α as an anticancer drug, using Fucci-based time lapse imaging, which will be informative for treating HCC with IFN-α in clinical practice. 相似文献
995.
Yoko Akaike Kiyoshi Masuda Yuki Kuwano Kensei Nishida Keisuke Kajita Ken Kurokawa Yuzuru Satake Katsutoshi Shoda Issei Imoto Kazuhito Rokutan 《Molecular and cellular biology》2014,34(15):2857-2873
Hu antigen R (HuR) regulates stress responses through stabilizing and/or facilitating the translation of target mRNAs. The human TRA2β gene encodes splicing factor transformer 2β (Tra2β) and generates 5 mRNA isoforms (TRA2β1 to -5) through alternative splicing. Exposure of HCT116 colon cancer cells to sodium arsenite stimulated checkpoint kinase 2 (Chk2)- and mitogen-activated protein kinase p38 (p38MAPK)-mediated phosphorylation of HuR at positions S88 and T118. This induced an association between HuR and the 39-nucleotide (nt) proximal region of TRA2β exon 2, generating a TRA2β4 mRNA that includes exon 2, which has multiple premature stop codons. HuR knockdown or Chk2/p38MAPK double knockdown inhibited the arsenite-stimulated production of TRA2β4 and increased Tra2β protein, facilitating Tra2β-dependent inclusion of exons in target pre-mRNAs. The effects of HuR knockdown or Chk2/p38MAPK double knockdown were also confirmed using a TRA2β minigene spanning exons 1 to 4, and the effects disappeared when the 39-nt region was deleted from the minigene. In endogenous HuR knockdown cells, the overexpression of a HuR mutant that could not be phosphorylated (with changes of serine to alanine at position 88 [S88A], S100A, and T118A) blocked the associated TRA2β4 interaction and TRA2β4 generation, while the overexpression of a phosphomimetic HuR (with mutations S88D, S100D, and T118D) restored the TRA2β4-related activities. Our findings revealed the potential role of nuclear HuR in the regulation of alternative splicing programs under oxidative stress. 相似文献
996.
Tetsuya Yamada Yoshihiro Mori Kazuho Yasue Nobuyuki Maruyama Keisuke Kitamura Jun Abe 《Plant cell reports》2014,33(12):1963-1976
Key message
A platform of gene silencing by amiRNA had been established in fertile transgenic soybean. We demonstrated that knockdown of storage protein shifted the distribution of nitrogen sources in soybean seeds.Abstract
Artificial microRNAs (amiRNAs) were designed using the precursor sequence of the endogenous soybean (Glycine max L. Merrill) miRNA gma-miR159a and expressed in transgenic soybean plants to suppress the biosynthesis of 7S globulin, which is one of the major storage proteins. Seed-specific expression of these amiRNAs (amiR-7S) resulted in a strong suppression of 7S globulin subunit genes and decreased accumulation of the 7S globulin subunits in seeds. Thus, the results demonstrate that a platform for gene silencing by amiRNA was first developed in fertile transgenic soybean plants. There was no difference in nitrogen, carbon, and lipid contents between amiR-7S and control seeds. Four protein fractions were collected from defatted mature seeds on the basis of solubility at different pH to examine the distribution of nitrogen sources and compensatory effects. In the whey and lipophilic fractions, nitrogen content was similar in amiR-7S and control seeds. Nitrogen content was significantly decreased in the major soluble protein fraction and increased in the residual fraction (okara) of the amiR-7S seeds. Amino acid analysis revealed that increased nitrogen compounds in okara were proteins or peptides rather than free amino acids. Our study indicates that the decrease in 7S globulin subunits shifts the distribution of nitrogen sources to okara in transgenic soybean seeds. 相似文献997.
Quan Xu Hiroki Saito Ikuo Hirose Keisuke Katsura Yoshihiro Yoshitake Takayuki Yokoo Takuji Tsukiyama Masayoshi Teraishi Takatoshi Tanisaka Yutaka Okumoto 《Molecular breeding : new strategies in plant improvement》2014,33(4):813-819
Flowering time is closely associated with grain yield in rice (Oryza sativa L.). In temperate regions, seasonal changes in day length (known as the photoperiod) are an important environmental cue for floral initiation. The timing of flowering is important not only for successful reproduction, but also for determining the ideal balance between vegetative growth and reproductive growth duration. Recent molecular genetics studies have revealed key flowering time genes responsible for photoperiod sensitivity. In this study, we investigated the effect of three recessive photoperiod-insensitive alleles, se13, hd1 and ghd7, on yield components in rice under Ehd1-deficient genetic background conditions to ensure vegetative growth of each line. We found that se13-bearing plants had fewer panicles, hd1-bearing plants showed decreased grain-filling percentage, and ghd7-bearing plants appeared to have fewer grains per panicle and fewer secondary branches. Our results indicate that the pleiotropic effects of photoperiod-insensitive genes on yield components are independent of short vegetative growth. This will provide critical information which can be used to create photoperiod-insensitive varieties that can be adapted to a wide range of latitudes. 相似文献
998.
999.
Objective
Enhancing structural and functional integrity of mitochondria is an emerging therapeutic option against endothelial dysfunction. In this study, we sought to investigate the effect of fluid shear stress on mitochondrial biogenesis and mitochondrial respiratory function in endothelial cells (ECs) using in vitro and in vivo complementary studies.Methods and Results
Human aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20 dyne/cm2) for various durations using a cone-and-plate shear apparatus. We observed significant increases in the expression of key genes related to mitochondrial biogenesis and mitochondrial quality control as well as mtDNA content and mitochondrial mass under the shear stress conditions. Mitochondrial respiratory function was enhanced when cells were intermittently exposed to laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished glycolysis and decreased mitochondrial membrane potential (ΔΨm). Likewise, in in vivo experiments, mice that were subjected to a voluntary wheel running exercise for 5 weeks showed significantly higher mitochondrial content determined by en face staining in the conduit (greater and lesser curvature of the aortic arch and thoracic aorta) and muscle feed (femoral artery) arteries compared to the sedentary control mice. Interestingly, however, the mitochondrial biogenesis was not observed in the mesenteric artery. This region-specific adaptation is likely due to the differential blood flow redistribution during exercise in the different vessel beds.Conclusion
Taken together, our findings suggest that exercise enhances mitochondrial biogenesis in vascular endothelium through a shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial pathway by which a chronic exercise may be beneficial for vascular function. 相似文献1000.
Masahide Usami Yoshitaka Iwadare Kyota Watanabe Masaki Kodaira Hirokage Ushijima Tetsuya Tanaka Maiko Harada Hiromi Tanaka Yoshinori Sasaki Seiko Okamoto Keisuke Sekine Kazuhiko Saito 《PloS one》2014,9(11)