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排序方式: 共有258条查询结果,搜索用时 109 毫秒
121.
Ryuta Kamekura Takashi Kojima Jun-ichi Koizumi Noriko Ogasawara Makoto Kurose Mitsuru Go Atsushi Harimaya Masaki Murata Satoshi Tanaka Hideki Chiba Tetsuo Himi Norimasa Sawada 《Cell and tissue research》2009,338(2):283-293
Epithelial-derived thymic stromal lymphopoietin (TSLP) triggers dendritic cell (DC)-mediated Th2-type inflammatory responses and is a master switch for allergic inflammatory diseases. In the present study, the expression and induction of TSLP and the effects of TSLP on the tight-junctional barrier of human nasal epithelial cells (HNECs) have been investigated in order to elucidate the role of TSLP in allergic rhinitis. We have found high expression of TSLP in the epithelium from patients with allergic rhinitis with recruitment and infiltration of DCs. In vitro, TSLP is significantly produced in HNECs after treatment with a toll-like receptor 2 (TLR2) ligand, Pam3Cys-Ser-(Lys)4, and a mixture of interleukin-1β and tumor necrosis factor-α. Treatment with TSLP rapidly enhances the barrier function of cultured HNECs, together with an increase of tight-junction proteins claudin-1, -4, -7, and occludin. The nasal-epithelial-derived TSLP thus not only activates DCs but also preserves the epithelial barrier via the upregulation of tight-junction proteins, thereby regulating antigen sensitization during the early stage of allergic rhinitis. 相似文献
122.
Ryuta Aoki Yohei Hayashi Koji Okabayashi Kiyoshi Ohnuma Masayuki Murata 《Biochemical and biophysical research communications》2010,400(2):200-206
Chromatin fluidity, which is one of the indicators of higher-order structures in chromatin, is associated with cell differentiation. However, little is known about the relationships between chromatin fluidity and cell differentiation status in embryonic development. We established an in vitro reconstitution system that uses isolated nuclei and cytoplasmic extracts of Xenopus embryos and a fluorescence recovery after photobleaching assay to measure the fluidities of heterochromatin protein 1 (HP1) and histone H1 during development. The HP1 and H1 fluidities of nuclei isolated from the tailbuds of early tadpole stage (stage 32) embryos in the cytoplasmic extracts of eggs and of late blastula stage (stage 9) embryos were higher than those in the cytoplasmic extracts of mid-neurula stage (stage 15) embryos. The HP1 fluidities of nuclei isolated from animal cap cells of early gastrula stage (stage 10) embryos and from the neural plates of neural stage (stage 20) embryos were higher than those isolated from the tailbuds of stage 32 embryos in egg extracts, whereas the HP1 fluidities of these nuclei were the same in the cytoplasmic extracts of stage 15 embryos. These results suggest that chromatin fluidity is dependent upon both cytoplasmic and nuclear factors and decreases during development. 相似文献
123.
Presenilin-1 and nicastrin, two components of gamma-secretase associated with Alzheimer's disease plaques, are present in the synapses of the brain and in various peripheral organs, including skeletal muscle. In the present study, we examined the expression pattern of presenilin-1 and nicastrin in normal and denervated hindlimb muscles of the rat. Using immunohistochemical approaches, we found that presenilin-1 and AChRalpha was co-localized at the neuromuscular junction in the normal skeletal muscles of rats. The immunoreactivities of both presenilin-1 and nicastrin were also observed at the sarcolemma of muscle fibers. We discovered that presenilin-1 mRNA and its protein are upregulated after denervation of the soleus and tibialis anterior muscles. Furthermore, clear co-localization between presenilin-1 and DAPI, but not nicastrin, was noted in several myonuclei in the denervated muscles. We recognized a few fibers possessing both ubiquitin and presenilin-1 protein in the cytosol. The amount of presenilin-1 in the nucleus and membrane fraction was more abundantly expressed in the denervated muscle fibers. In contrast, no significant difference in the nicastrin protein level was observed between normal and denervated muscle fibers. These data suggest that enhanced presenilin-1 protein may play a role in the degeneration and regeneration of skeletal muscle. 相似文献
124.
Crystal structure of west nile virus envelope glycoprotein reveals viral surface epitopes 总被引:6,自引:0,他引:6
Kanai R Kar K Anthony K Gould LH Ledizet M Fikrig E Marasco WA Koski RA Modis Y 《Journal of virology》2006,80(22):11000-11008
West Nile virus, a member of the Flavivirus genus, causes fever that can progress to life-threatening encephalitis. The major envelope glycoprotein, E, of these viruses mediates viral attachment and entry by membrane fusion. We have determined the crystal structure of a soluble fragment of West Nile virus E. The structure adopts the same overall fold as that of the E proteins from dengue and tick-borne encephalitis viruses. The conformation of domain II is different from that in other prefusion E structures, however, and resembles the conformation of domain II in postfusion E structures. The epitopes of neutralizing West Nile virus-specific antibodies map to a region of domain III that is exposed on the viral surface and has been implicated in receptor binding. In contrast, we show that certain recombinant therapeutic antibodies, which cross-neutralize West Nile and dengue viruses, bind a peptide from domain I that is exposed only during the membrane fusion transition. By revealing the details of the molecular landscape of the West Nile virus surface, our structure will assist the design of antiviral vaccines and therapeutics. 相似文献
125.
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
126.
Shibata T Ariki S Shinzawa N Miyaji R Suyama H Sako M Inomata N Koshiba T Kanuka H Kawabata S 《PloS one》2010,5(10):e13477
Transglutaminase (TG) plays important and diverse roles in mammals, such as blood coagulation and formation of the skin barrier, by catalyzing protein crosslinking. In invertebrates, TG is known to be involved in immobilization of invading pathogens at sites of injury. Here we demonstrate that Drosophila TG is an important enzyme for cuticle morphogenesis. Although TG activity was undetectable before the second instar larval stage, it dramatically increased in the third instar larval stage. RNA interference (RNAi) of the TG gene caused a pupal semi-lethal phenotype and abnormal morphology. Furthermore, TG-RNAi flies showed a significantly shorter life span than their counterparts, and approximately 90% of flies died within 30 days after eclosion. Stage-specific TG-RNAi before the third instar larval stage resulted in cuticle abnormality, but the TG-RNAi after the late pupal stage did not, indicating that TG plays a key role at or before the early pupal stage. Immediately following eclosion, acid-extractable protein from wild-type wings was nearly all converted to non-extractable protein due to wing maturation, whereas several proteins remained acid-extractable in the mature wings of TG-RNAi flies. We identified four proteins--two cuticular chitin-binding proteins, larval serum protein 2, and a putative C-type lectin-as TG substrates. RNAi of their corresponding genes caused a lethal phenotype or cuticle abnormality. Our results indicate that TG-dependent protein crosslinking in Drosophila plays a key role in cuticle morphogenesis and sclerotization. 相似文献
127.
Seiga Ohmine Ryuta Sakuma Toshie Sakuma Tayaramma Thatava Gonzalo P. Solis Yasuhiro Ikeda 《The Journal of biological chemistry》2010,285(45):34508-34517
TRIM5α is a member of the tripartite motif (TRIM) family of proteins and affects both early and late phases of the retroviral life cycle. Although TRIM5α multimerizes to form cytoplasmic bodies, which are thought to play an important role in viral restriction, the identity of TRIM5α-containing cytoplasmic bodies remains elusive. To better understand TRIM5α cytoplasmic body constituents and the cellular proteins that could be involved in the TRIM5α-mediated antiviral activities, we sought TRIM5α-binding factors. We identified a lipid microdomain protein flotillin-1/Reggie-2 as an interacting partner of TRIM5α via co-immunoprecipitation. Immunohistochemistry studies confirmed the co-localization of rhesus monkey TRIM5α (TRIM5αrh) cytoplasmic bodies with flotillin-1/Reggie-2. Caveolin-1, another lipid microdomain-associated protein, also co-localized with TRIM5α cytoplasmic bodies. Intriguingly, disruption of cellular cholesterol by cyclodextrin perturbed TRIM5α cytoplasmic body formation. Furthermore, lipid starvation partially relieved the endogenous post-entry restriction of HIV-1 infection, which could be subsequently restored by lipid repletion. These observations indicate the involvement of cellular lipids in TRIM5α-mediated antiviral activities. Given that many viruses utilize cellular lipid microdomains for viral entry and assembly, it is plausible that lipid-enriched domains provide microenvironments where TRIM5α recognizes retroviral components. 相似文献
128.
Ryuta Kamekura Takashi Kojima Akira Takashima Jun-ichi Koizumi Noriko Ogasawara Mitsuru Go Ken-ichi Takano Masaki Murata Satoshi Tanaka Shingo Ichimiya Tetsuo Himi Norimasa Sawada 《Histochemistry and cell biology》2010,133(3):339-348
Epithelial-derived thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine that triggers dendritic cell (DC)-mediated Th2-type inflammatory responses. The activated DCs can penetrate the epithelium to directly take up antigen without compromising the barrier function. Although it is reported that DCs express tight junction molecules and can establish tight junction-like structures with adjacent epithelial cells to preserve the epithelial barrier, the regulation of expression of tight junction molecules in DCs remains unknown. In the present study, to investigate the mechanical regulation of expression of tight junction molecules in DCs, XS52 DCs that was a long-term DC line established from the epidermis of a newborn BALB/c mouse, were treated with TSLP or toll-like receptor (TLR) ligands. In XS52 cells, tight junction molecules claudin-1, -3, -4, -6, -7, -8, and occludin were detected. mRNA expression of TSLP receptor and all these tight junction molecules was significantly increased in activated XS52 cells after treatment with TSLP. In addition, expression of claudin-7 protein was increased in dose- and time-dependent manner. In XS52 cells, which express TLR2, TLR3, TLR4, and TLR7, but not TLR9, expression of claudin-7 protein was also increased after treatment with ligands of TLR2, TLR4 or TLR7/8, Pam3Cys-Ser-(Lys)4, LPS, or CL097. The NF-κB inhibitor IMD-0354 prevented upregulation of claudin-7 after treatment with TSLP or TLR ligands. These findings indicate that TSLP induces expression of tight junction protein claudin-7 in DCs via NF-κB as well as via TLRs and may control tight junctions of DCs to preserve the epithelial barrier during allergic inflammation. 相似文献
129.
Ryuta Terada Yuto Nakashima Iris Ann Borlongan Hiromori Shimabukuro Jumpei Kozono Hikaru Endo Satoshi Shimada Gregory N. Nishihara 《Phycological Research》2020,68(1):70-79
The effects of irradiance, temperature, thermal‐ and chilling‐light sensitivities on the photosynthesis of a temperate alga, Sargassum macrocarpum (Fucales) were determined by a pulse amplitude modulation (PAM)‐chlorophyll fluorometer and dissolved oxygen sensors. Oxygenic photosynthesis–irradiance curves at 8, 20, and 28°C revealed that the maximum net photosynthetic rates (NP max) and saturation irradiance were highest at 28°C, and lowest at 8°C. Gross photosynthesis and dark respiration determined over a range of temperatures (8–36°C) at 300 μmol photons m?2 s?1 revealed that the maximum gross photosynthetic rate (GPmax) occurred at 27.8°C, which is consistent with the highest seawater temperature in the southern distributional limit of this species in Japan. Additionally, the maximum quantum yields of photosystem II (F v/F m) during the 72‐h temperature exposures were stable at 8–28°C, but suddenly dropped to zero at higher temperatures, indicative of PSII deactivation. Continuous exposure (12 h) to irradiance of 200 (low) and 1000 (high) μmol photons m?2 s?1 at 8, 20, and 28°C revealed greater declines in their effective quantum yields (Φ PSII) under high irradiance. While Φ PSII under low irradiance were very similar with the initial F v/F m under 20 and 28°C, values rapidly decreased with exposure duration at 8°C. At this temperature, F v/F m did not recover to initial values even after 12 h of dark acclimation. Final F v/F m of alga at 28°C under high irradiance treatment also did not recover, suggesting its sensitivity to photoinhibition at both low and high temperatures. These photosynthetic characteristics reflect both the adaptation of the species to the general environmental conditions, and its ability to acclimate to seasonal changes in seawater temperature within their geographical range of distribution. 相似文献
130.
Jun Matsuda Atsushi Takahashi Yoshitsugu Takabatake Shinsuke Sakai Satoshi Minami Takeshi Yamamoto Ryuta Fujimura Tomoko Namba-Hamano Hiroaki Yonishi Jun Nakamura Tomonori Kimura Jun-Ya Kaimori Isao Matsui Masatomo Takahashi Motonao Nakao Yoshihiro Izumi Takeshi Bamba Taiji Matsusaka Fumio Niimura Motoko Yanagita Tamotsu Yoshimori Yoshitaka Isaka 《Autophagy》2020,16(10):1889