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91.
Toya M Hozumi Y Ito T Takeda M Sakane F Kanoh H Saito H Hiroi M Kurachi H Kondo H Goto K 《Cell and tissue research》2005,320(3):525-533
Female reproductive organs show remarkable cyclic changes in morphology and function in response to a combination of hormones. Evidence has accumulated suggesting that phosphoinositide turnover and the consequent diacylglycerol (DG) protein kinase C (PKC) pathway are intimately involved in these mechanisms. The present study has been performed to investigate the gene expression, cellular localization, and enzymatic activity of the DG kinase (DGK) isozymes that control the DG-PKC pathway. Gene expression for DGK, -, -, and - was detected in the ovary and placenta. Intense expression signals for DGK and - were observed in the theca cells and moderate signals in the interstitium and corpora lutea of the ovary. On the other hand, signals for DGK were seen more intensely in granulosa cells. In the placenta, signals for DGK and - were observed in the junctional zone, whereas those for DGK were detected in the labyrinthine zone. At higher magnification, the signals for DGK were mainly discerned in giant cytotrophoblasts, and those for DGK were found in small cytotrophoblasts of the junctional zone. DGK signals were observed in all cellular components of the labyrinthine zone, including mesenchyme, trabecular trophoblasts, and cytotrophoblasts. DGK signals were detected in the junctional zone on day 13 and 15 of pregnancy and were diffusely distributed both in the labyrinthine and junctional zones at later stages. The present study reveals distinct patterns of mRNA localization for DGK isozymes in the rat ovary and placenta, suggesting that each isozyme plays a unique role in distinct cell types in these organs.This work was supported by Grants-in-Aids from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, the Uehara Memorial Foundation, the ONO Medical Research Foundation, the Ciba-Geigy Foundation (Japan) for the Promotion of Science, the Kato Memorial Bioscience Foundation, and the Yamagata Health Support Foundation (to K.G.). 相似文献
92.
Murakami M Masuda S Ueda-Semmyo K Yoda E Kuwata H Takanezawa Y Aoki J Arai H Sumimoto H Ishikawa Y Ishii T Nakatani Y Kudo I 《The Journal of biological chemistry》2005,280(14):14028-14041
Although group VIA Ca2+-independent phospholipase A2beta (iPLA2beta) has been implicated in various cellular events, the functions of other iPLA2 isozymes remain largely elusive. In this study, we examined the cellular functions of group VIB iPLA2gamma. Lentiviral transfection of iPLA2gamma into HEK293 cells resulted in marked increases in spontaneous, stimulus-coupled, and cell death-associated release of arachidonic acid (AA), which was converted to prostaglandin E2 with preferred cyclooxygenase (COX)-1 coupling. Conversely, treatment of HEK293 cells with iPLA2gamma small interfering RNA significantly reduced AA release, indicating the participation of endogenous iPLA2gamma. iPLA2gamma protein appeared in multiple sizes according to cell types, and a 63-kDa form was localized mainly in peroxisomes. Electrospray ionization mass spectrometry of cellular phospholipids revealed that iPLA2gamma and other intracellular PLA2 enzymes acted on different phospholipid subclasses. Transfection of iPLA2gamma into HCA-7 cells also led to increased AA release and prostaglandin E2 synthesis via both COX-1 and COX-2, with a concomitant increase in cell growth. Immunohistochemistry of human colorectal cancer tissues showed elevated expression of iPLA2gamma in adenocarcinoma cells. These results collectively suggest distinct roles for iPLA2beta and iPLA2gamma in cellular homeostasis and signaling, a functional link between peroxisomal AA release and eicosanoid generation, and a potential contribution of iPLA2gamma to tumorigenesis. 相似文献
93.
Adachi Y Lakka SS Chandrasekar N Yanamandra N Gondi CS Mohanam S Dinh DH Olivero WC Gujrati M Tamiya T Ohmoto T Kouraklis G Aggarwal B Rao JS 《The Journal of biological chemistry》2001,276(50):47171-47177
Interaction between the extracellular matrix and integrin receptors on cell surfaces leads not only to cell adhesion but also to intracellular signaling events that affect cell migration, proliferation, and survival. The vitronectin receptor alpha(v)beta(3) integrin is of key importance in glioma cell biology. The expression of urokinase-type plasminogen activator receptor (uPAR) was recently shown to co-regulate with the expression of alpha(v)beta(3) integrin. Moreover, restoration of the p16 protein in glioma cells inhibits the alpha(v)beta(3) integrin-mediated spreading of those cells on vitronectin. Thus we hypothesized that adenovirus-mediated down-regulation of uPAR and overexpression of p16 might down-regulate the expression of alpha(v)beta(3) integrin and the integrin-mediated signaling in glioma cells, thereby defeating the malignant phenotype. In this study, we used replication-deficient adenovirus vectors that contain either a uPAR antisense expression cassette (Ad-uPAR) or wild-type p16 cDNA (Ad-p16) and a bicistronic adenovirus construct in which both the uPAR antisense and p16 sense expression cassettes (Ad-uPAR/p16) are inserted in the E1-deleted region of the vector. Infecting the malignant glioma cell line SNB19 with Ad-uPAR, Ad-p16, or Ad-uPAR/p16 in the presence of vitronectin resulted in decreased alpha(v)beta(3) integrin expression and integrin-mediated biological effects, including adhesion, migration, proliferation, and survival Our results support the therapeutic potential of simultaneously targeting uPAR and p16 in the treatment of gliomas. 相似文献
94.
Mizunuma M Yamada Y Yamada K Sonta S Wakamatsu N Kaneko K Ogasawara N Fujimori S 《Nucleosides, nucleotides & nucleic acids》2004,23(8-9):1173-1176
In this study, we have identified a novel mechanism of mutation involving translocation between the HPRT1 loci and other loci on the X chromosome. In HRT-25's cDNA obtained from a patient with Lesch-Nyhan syndrome, the upstream region of exon 3 was amplified, but the full-length region was not amplified. The use of 3' rapid amplification of cDNA ends polymerase chain reaction (3'RACE-PCR) for HRT-25 revealed part of intron 3 and an unknown sequence which have not identified the HPRT1 gene starting at the 3' end of exon 3. We analyzed HPRT1 genomic DNA in order to confirm the mutation with the unknown sequence in the genomic DNA. Unknown sequence compared through BLAST analysis of human genome (NCBI; http://www.ncbi.nlm.nih.gov/BLAST/) showed that at least 0.5 to 0.6-Mb telomeric to HPRT1 on chromosome Xq where located near LOC340581. This study provides the molecular basis for the involvement of genomic instability in germ cells. 相似文献
95.
Eizo Hayatsu Yasuaki Kawakubo Masumi Yayoshi Minako Araake Morimasa Yoshioka Yasukazu Nishiyama 《Microbiology and immunology》1980,24(7):585-593
Golden Syrian hamsters adoptively immunized with hyperimmune Mycoplasma pneumoniae rabbit antiserum, immunoglobulin (Ig) M-rich (IgM) fraction, IgG-rich (IgG) fraction, antiserum absorbed with either killed M. pneumoniae or killed Staphylococcus aureus organisms, or antiserum treated with 2-mercaptoethanol (2-ME) were examined for resistance against aerosol infection with virulent M. pneumoniae. Significant resistance to the establishment of infection in the respiratory tract was shown in hamsters pretreated with the untreated antiserum, IgG fraction or 2-ME-treated antiserum, whereas animals pretreated with the IgM fraction and the antisera absorbed with M. pneumoniae or S. aureus organisms were not significantly resistant. Histopathologically, lung lesions were markedly suppressed in animals with high resistance, but were typically pneumonic in animals with low or no resistance. The efficacy of adoptively administered serum preparations was closely related to their antibody titers. The results indicate that humoral antibody plays an important role in protection against experimental M. pneumoniae pneumonia in hamsters, although the participation of the cell-mediated immune response was not determined. 相似文献
96.
97.
Hiroshi Fukushima Minato Yokoyama Yasukazu Nakanishi Ken-ichi Tobisu Fumitaka Koga 《PloS one》2015,10(1)
Objectives
Sarcopenia, a novel concept reflecting the degenerative loss of skeletal muscle mass, is an objective indicator of cancer cachexia. We investigated its role as a prognostic biomarker in advanced urothelial carcinoma (UC) patients.Methods
This retrospective study consisted of 88 UC patients with cT4 and/or metastases to lymph nodes/distant organs. Skeletal muscle index (SMI), an indicator of whole-body muscle mass, was measured from computed tomography (CT) images at the diagnosis. Sarcopenia was defined as SMIs of <43 cm2/m2 for males with body mass index (BMI) <25 cm2/m2, <53 cm2/m2 for males with BMI ≥25 cm2/m2, and <41 cm2/m2 for females. Predictors of overall survival (OS) were examined using Cox proportional hazard models.Results
Sixty-seven patients (76%) died during the median follow-up of 13 months. The median OS rate was 13 months. Multivariate analysis revealed that SMI was a significant and independent predictor of shorter OS (hazard ratio (HR) 0.90, P <0.001). In the present cohort, 53 (60%) were diagnosed with sarcopenia. The median OS rates were 11 and 31 months for sarcopenic and non-sarcopenic patients, respectively (P <0.001). On multivariate analysis, sarcopenia was a significant and independent predictor of shorter OS (HR 3.36, P <0.001), along with higher C-reactive protein (CRP) (P = 0.001), upper urinary tract cancer (P = 0.007), higher lactate dehydrogenase (LDH) (P = 0.047), and higher alkaline phosphatase (ALP) (P = 0.048).Conclusion
Sarcopenia, which is readily evaluated on routine CT scans, is a useful prognostic biomarker of advanced UC. Non-sarcopenic patients can expect long-term survival. Evaluating sarcopenia can be helpful for decision-making processes in the management of advanced UC patients. 相似文献98.
99.
Hideki Nagasaki Takako Mochizuki Yuichi Kodama Satoshi Saruhashi Shota Morizaki Hideaki Sugawara Hajime Ohyanagi Nori Kurata Kousaku Okubo Toshihisa Takagi Eli Kaminuma Yasukazu Nakamura 《DNA research》2013,20(4):383-390
High-performance next-generation sequencing (NGS) technologies are advancing genomics and molecular biological research. However, the immense amount of sequence data requires computational skills and suitable hardware resources that are a challenge to molecular biologists. The DNA Data Bank of Japan (DDBJ) of the National Institute of Genetics (NIG) has initiated a cloud computing-based analytical pipeline, the DDBJ Read Annotation Pipeline (DDBJ Pipeline), for a high-throughput annotation of NGS reads. The DDBJ Pipeline offers a user-friendly graphical web interface and processes massive NGS datasets using decentralized processing by NIG supercomputers currently free of charge. The proposed pipeline consists of two analysis components: basic analysis for reference genome mapping and de novo assembly and subsequent high-level analysis of structural and functional annotations. Users may smoothly switch between the two components in the pipeline, facilitating web-based operations on a supercomputer for high-throughput data analysis. Moreover, public NGS reads of the DDBJ Sequence Read Archive located on the same supercomputer can be imported into the pipeline through the input of only an accession number. This proposed pipeline will facilitate research by utilizing unified analytical workflows applied to the NGS data. The DDBJ Pipeline is accessible at http://p.ddbj.nig.ac.jp/. 相似文献
100.
Yukitake H Kimura H Suzuki H Tajima Y Sato Y Imaeda T Kajino M Takizawa M 《PloS one》2011,6(8):e23256
Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that are primarily represented by ulcerative colitis and Crohn's disease. The etiology of IBD is not well understood; however, oxidative stress is considered a potential etiological and/or triggering factor for IBD. We have recently reported the identification of BTZO-1, an activator of antioxidant response element (ARE)-mediated gene expression, which protects cardiomyocytes from oxidative stress-induced insults. Here we describe the potential of BTZO-15, an active BTZO-1 derivative for ARE-activation with a favorable ADME-Tox profile, for the treatment of IBD. BTZO-15 induced expression of heme oxygenase-1 (HO-1), an ARE-regulated cytoprotective protein, and inhibited NO-induced cell death in IEC-18 cells. Large intestine shortening, rectum weight gain, diarrhea, intestinal bleeding, and an increase in rectal myeloperoxidase (MPO) activity were observed in a dextran sulfate sodium (DSS)-induced colitis rat model. Oral administration of BTZO-15 induced HO-1 expression in the rectum and attenuated DSS-induced changes. Furthermore BTZO-15 reduced the ulcerated area and rectal MPO activity in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats without affecting rectal TNF-α levels. These results suggest that BTZO-15 is a promising compound for a novel IBD therapeutic drug with ARE activation properties. 相似文献