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排序方式: 共有207条查询结果,搜索用时 343 毫秒
91.
S Nasu F D Wicks S Sakakibara R K Gholson 《Biochemical and biophysical research communications》1978,84(4):928-935
Two proteins (A and B) from are required for the synthesis of the NAD precursor quinolinate from aspartate and dihydroxyacetone phosphate. Mammalian liver contains a FAD linked protein which replaces B protein for quinolinate synthesis. D-aspartic acid but not L-aspartic acid is a substrate for quinolinic acid synthesis in a system composed of the B protein replacing activity of mammalian liver and A protein. In contrast the B protein- A protein quinolinate synthetase system requires L-aspartic acid as substrate. The previous report that L-aspartate was a substrate in the liver- system was due to contamination of commercially available [14C]L-aspartate with [14C]D-aspartate. These and other observations suggest that liver B protein is D-aspartate oxidase and B protein is L-aspartate oxidase. 相似文献
92.
Ohne ZusammenfassungMit 3 TextabbildungenDurchgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft.Assistent an der Neurochirurgischen Universitätsklinik Genua; z. Z. Stipendiat der Max Planck-Gesellschaft. 相似文献
93.
Solar Cells: π‐Extended Narrow‐Bandgap Diketopyrrolopyrrole‐Based Oligomers for Solution‐Processed Inverted Organic Solar Cells (Adv. Energy Mater. 17/2014) 下载免费PDF全文
94.
A new means of rapidly and simultaneously counting viable phylogenetically different bacteria was developed. The cyanine dimer dye, BOBO-3 that selectively stains bacteria with damaged membranes were used to evaluate bacterial viability based on membrane integrity. Viable Enterobacteriaceae and Pseudomonas spp. could be selectively detected within three hours using multicolor fluorescence in situ hybridization (FISH) following BOBO-3 staining (BOBO3-FISH). 相似文献
95.
Masakiyo Sakaguchi Ken Kataoka Fernando Abarzua Ryuta Tanimoto Masami Watanabe Hitoshi Murata Swe Swe Than Kaoru Kurose Yuji Kashiwakura Kazuhiko Ochiai Yasutomo Nasu Hiromi Kumon Nam-ho Huh 《The Journal of biological chemistry》2009,284(21):14236-14244
We previously showed that the tumor suppressor gene
REIC/Dkk-3, when overexpressed by an adenovirus (Ad-REIC),
exhibited a dramatic therapeutic effect on human cancers through a mechanism
triggered by endoplasmic reticulum stress. Adenovirus vectors show no target
cell specificity and thus may elicit unfavorable side effects through
infection of normal cells even upon intra-tumoral injection. In this study, we
examined possible effects of Ad-REIC on normal cells. We found that infection
of normal human fibroblasts (NHF) did not cause apoptosis but induced
production of interleukin (IL)-7. The induction was triggered by endoplasmic
reticulum stress and mediated through IRE1α, ASK1, p38, and IRF-1. When
Ad-REIC-infected NHF were transplanted in a mixture with untreated human
prostate cancer cells, the growth of the cancer cells was significantly
suppressed. Injection of an IL-7 antibody partially abrogated the suppressive
effect of Ad-REIC-infected NHF. These results indicate that Ad-REIC has
another arm against human cancer, an indirect host-mediated effect because of
overproduction of IL-7 by mis-targeted NHF, in addition to its direct effect
on cancer cells.Cancer cells, like normal cells, cannot be free from regulation by other
cells in the body (1). The
microenvironment can exert both promotive and suppressive effects on malignant
cells (2). The embryonic
environment has been shown to suppress malignant phenotypes
(3,
4), and this was recently
indicated to be due to suppression of Nodal function by Lefty
(5). Cells comprising cancer
stroma in adult tissues are also involved in tumor suppression
(6,
7). Mobilization of such
potential tumor-suppressive effects of the microenvironment would provide an
additional arm for cancer therapy
(8).Adenovirus vectors combined with appropriate cargo genes have great
potential in cancer gene therapy because of their high infection efficiency
and marginal genotoxicity (9).
However, they show no target cell specificity and thus may also infect normal
cells present in the surroundings of cancer cells. Provided that the
interaction between cancer cells and normal cells is relevant to
progression/suppression of cancer, it is critically important to understand
not only cell autonomous phenomena in individual cell types infected by a
therapeutic virus vector but also potential effects of the therapeutic virus
vector on the composite system of interacting cell populations.We have been studying the possible utility of an adenovirus vector carrying
the tumor suppressor gene REIC/Dkk-3 (Ad-REIC) for gene
therapy against human cancer. REIC/Dkk-3 was first
identified as a gene that was down-regulated in association with
immortalization of normal human fibroblasts
(NHF)2
(10). Expression of
REIC/Dkk-3 gene was shown to be reduced in many human cancer
cells and tissues, including prostate cancer, renal clear cell carcinoma,
testicular cancer, and non-small cell lung cancer
(11–14),
probably due to hypermethylation of the promoter
(15). A single injection of
Ad-REIC into tumors formed by transplantation of human prostate cancer cells
(PC3 cells) into mice resulted in 4 of 5 mice becoming tumor-free
(13). Subsequently, we found
that Ad-REIC was effective also for human cancers derived from the testis,
pleura, and breast (14,
16,
17). The potent multitargeting
anti-cancer function of Ad-REIC shows great promise for clinical application,
which will be shortly initiated.REIC/Dkk-3 is a highly glycosylated secretory protein and
is considered to physiologically act on cells via a yet-unidentified receptor.
However, we found that the induction of apoptosis in cancer cells by Ad-REIC
was because of endoplasmic reticulum (ER) stress loaded by overproduction of
the REIC/Dkk-3 protein and that exogenously applied REIC/Dkk-3 protein showed
no apoptosis inducing activity for cancer cells
(13,
14). Activation of c-Jun
N-terminal kinase (JNK) was shown to be an essential step for the induction of
apoptosis by Ad-REIC. ER stress is evoked by overload of unfolded/misfolded
proteins in the ER, and eukaryotic cells respond to the threat by activating
an unfolded protein response, i.e. attenuating de novo
protein synthesis, promoting protein degradation by proteasomes, and inducing
chaperone proteins to help proper folding of proteins
(18). When ER stress remains
at a level manageable by the unfolded protein response, cells can survive. On
the other hand, overload of unfolded/misfolded protein beyond the cellular
adoptive response leads to apoptotic cell death. Although Ad-REIC strongly
induces apoptosis in many types of cancer cells, normal cells thus far
examined are resistant to Ad-REIC-induced apoptosis despite expression of
REIC/Dkk-3 at a level similar to that in cancer cells
(13). The aim of this study
was to determine the mechanisms of differential response of normal cells and
cancer cells to Ad-REIC and to reveal the possible effect of Ad-REIC on a
composite interacting system of normal cells and cancer cells. We found that
Ad-REIC induced NHF to produce IL-7 via ER stress-triggered activation of p38.
Furthermore, Ad-REIC-infected NHF significantly suppressed tumor growth of
untreated PC3 cells transplanted in a mixture in vivo. These results
mean that, in addition to its direct cancer cell-killing activity, Ad-REIC has
another mechanism of action against human cancer, an indirect host-mediated
effect because of overproduction of IL-7 by mis-targeted NHF. 相似文献
96.
Taka Nakahara Yuichi Tamaki Noriko Tominaga Yoshiaki Ide Masanori Nasu Akihiro Ohyama Soh Sato Isamu Ishiwata Hiroshi Ishikawa 《Human cell》2010,23(1):15-25
Novel cell lines, designated NM78-AM and NM78-MM, have been established from a malignant melanoma of the cheek oral mucosa. NM78-AM cells were spherical, grew in suspension as clusters, and produced no melanin. In contrast, NM78-MM cells were adherent and produced melanin granules. Initially, NM78-AM cells were grown on fibroblast feeder cells or in growth media supplemented with 10% conditioned medium from fibroblasts, but eventually grew in standard growth media alone. NM78-AM cells had interdigitating microvilli and formed cell clusters. They had large nucleoli, desmosomes, lipid droplets, and well-developed Golgi apparatuses. In contrast, NM78-MM cells grew as adherent neuron-like cells. They had large prominent nucleoli, irregular nuclear membranes, a number of mitochondria, well-developed Golgi apparatuses, melanosomes at various stages of development in the cytoplasm, and the cells secreted melanin granules. Projections from these melanotic cells formed anastomoses with each other. NM78-MM cells stained immunofluorescently for internexin, neuron specific enolase, NF-200, and glial fibrillary acidic protein. These cells were severely aneuploid, approximating to triploidy, and had many marker chromosomes. We used a real-time monitoring system to evaluate oxygen concentrations in culture medium to investigate the susceptibility of both cell lines to various anti-cancer drugs. NM78-AM cells were slightly sensitive to actinomycin D, but not to cisplatin, irinotecan, the irinotecan metabolite SN-38, taxol, taxotere, bleomycin and methotrexate; NM78-MM cells were sensitive to cisplatin, and not to taxol, taxotere, carboplatin, and irinotecan. These new cell lines, NM78-AM and NM78-MM, will be very important for the development of new chemotherapeutics for oral malignant melanoma. 相似文献
97.
98.
Ochiai K Watanabe M Ueki H Huang P Fujii Y Nasu Y Noguchi H Hirata T Sakaguchi M Huh NH Kashiwakura Y Kaku H Kumon H 《Biochemical and biophysical research communications》2011,(2):391-395
REIC/Dkk-3 is a member of the Dickkopf family proteins known as Wnt-antagonists, and REIC/Dkk-3 expression is downregulated in a broad range of cancer types. REIC/Dkk-3 acts as a tumor suppressor in multiple cancer cell lines by inducing apoptosis through endoplasmic reticulum (ER) stress signaling. However, the intracellular interaction partners of REIC/Dkk-3 have not been fully elucidated. By employing yeast two-hybrid screening, we identified the human dynein light chain, Tctex-1, as a novel interaction partner of REIC/Dkk-3. We further disclosed that the interaction involves the 136–157 amino acid region of REIC/Dkk-3 by using the mammalian two-hybrid system. Interestingly, this binding region of REIC/Dkk-3 with Tctex-1 contains an amino acid sequence motif [-E-X-G-R-R-X-H-] which was previously reported as the Tctex-1 binding domain of dynein intermediate chain (DIC). Immunocytochemistry demonstrated that both REIC/Dkk-3 and Tctex-1 were localized around the ER of human fibroblasts, and the similar distribution pattern of the proteins suggests that their interaction occurs around the ER. This is the first study showing the interaction of a Dickkopf family protein with a dynein motor complex protein. The link between REIC/Dkk-3 and Tctex-1 may be of significance for understanding the molecular functions of the proteins in ER stress signaling and intracellular dynein motor dynamics, respectively. 相似文献
99.
Saito D Maeshima Y Nasu T Yamasaki H Tanabe K Sugiyama H Sonoda H Sato Y Makino H 《American journal of physiology. Renal physiology》2011,300(4):F873-F886
The involvement of VEGF-A as well as the therapeutic efficacy of angiogenesis inhibitors in diabetic nephropathy have been reported. We recently reported the therapeutic effects of vasohibin-1 (VASH-1), an endogenous angiogenesis inhibitor, in a type 1 diabetic nephropathy model (Nasu T, Maeshima Y, Kinomura M, Hirokoshi-Kawahara K, Tanabe K, Sugiyama H, Sonoda H, Sato Y, Makino H. Diabetes 58: 2365-2375, 2009). In this study, we investigated the therapeutic efficacy of VASH-1 on renal alterations in obese mice with type 2 diabetes. Diabetic db/db mice received intravenous injections of adenoviral vectors encoding human VASH-1 (AdhVASH-1) and were euthanized 8 wk later. AdhVASH-1 treatment resulted in significant suppression of glomerular hypertrophy, glomerular hyperfiltration, albuminuria, increase in the CD31(+) glomerular endothelial area, F4/80(+) monocyte/macrophage infiltration, the accumulation of type IV collagen, and mesangial matrix. An increase in the renal levels of VEGF-A, VEGFR-2, transforming growth factor (TGF)-β1, and monocyte chemoattractant protein-1 in diabetic animals was significantly suppressed by AdhVASH-1 (immunoblotting). AdhVASH-1 treatment significantly recovered the loss and altered the distribution patterns of nephrin and zonula occludens (ZO)-1 and suppressed the increase in the number of fibroblast-specific protein-1 (FSP-1(+)) and desmin(+) podocytes in diabetic mice. In vitro, recombinant human VASH-1 (rhVASH-1) dose dependently suppressed the upregulation of VEGF induced by high ambient glucose (25 mM) in cultured mouse podocytes. In addition, rhVASH-1 significantly recovered the mRNA levels of nephrin and the protein levels of ZO-1 and P-cadherin and suppressed the increase in protein levels of desmin, FSP-1, Snail, and Slug in podocytes under high-glucose condition. Taken together, these results suggest the potential use of VASH-1 as a novel therapeutic agent in type 2 diabetic nephropathy mediated via antiangiogenic effects and maintenance of podocyte phenotype in association with antiproteinuric effects. 相似文献
100.
Takeshi Ohkawara Akiko Oyabu Michiru Ida-Eto Yasura Tashiro Kaori Tano Fumio Nasu Naoko Narita Masaaki Narita 《International journal of peptide research and therapeutics》2011,17(3):193-199
The cerebellum has long been recognized as the primary center of motor coordination in the central nervous system. Cerebellar
neuropeptides have been postulated to be involved in such motor coordination, though this role is not fully understood. We
herein investigated the localization of novel neuropeptide, “manserin” in the adult rat cerebellum. Punctate signals of manserin
immunoreactivity were observed in the granular layer of the rat cerebellum. Manserin signals were also observed in the fibers
and fiber terminals in the granular layer as well as the molecular layer. Manserin did not localize in Purkinje cells. Interestingly,
cerebellar manserin was preferentially colocalized with unipolar brush cells, a class of excitatory granular layer interneuron,
which are known to be involved in vestibullocerebellar functions. These results indicate that manserin plays pivotal roles
in the cerebellar functions. 相似文献