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81.
Stress to endoplasmic reticulum of mouse osteoblasts induces apoptosis and transcriptional activation for bone remodeling 总被引:1,自引:0,他引:1
ATF4 is an essential regulator in osteogenesis as well as in stress responses to the endoplasmic reticulum (ER). We addressed a question: Does ER stress to osteoblasts upregulate ATF4 expression? If so, do they exhibit ATF4-mediated bone remodeling or apoptosis? ER stress, induced by Thapsigargin and tunicamycin, elevated a phosphorylated form of eIF2alpha and ATF4, but the cellular fate depended on treatment duration. The treatment for 1h, for instance, activated Runx2, and type I collagen, while the treatment for 24h induced apoptosis. Our observations suggest that there is a threshold for ER stress and osteoblasts present a bi-phasic pattern of their fate. 相似文献
82.
Watanabe H Shionyu M Kimura T Kimata K Watanabe H 《The Journal of biological chemistry》2007,282(28):20728-20738
Bone morphogenetic protein (BMP)-2/4 play critical roles in early embryogenesis and skeletal development. BMP-2/4 signals conduct into cells via two types of serine/threonine kinase receptors, known as BMPR-I (IA and IB) and BMPR-II. Here we identified splicing factor 3b subunit 4 (SF3b4) as a molecule that interacts with BMPR-IA, using a yeast two-hybrid screening with a human fetal brain cDNA library. Co-immunoprecipitation/immunoblot analysis confirmed their interaction in mammalian cells. By separation of the cell components, SF3b4 was present in the cell membrane fraction with BMPR-IA as well as in the nucleus. Overexpression of SF3b4 inhibited BMP-2-mediated osteogenic and chondrocytic differentiation of C2C12 and ATDC5 cells, respectively, and the endogenous expression level of SF3b4 decreased during differentiation in ATDC5 cells. By reporter gene assay, SF3b4 suppressed Id reporter gene activity, specific to the Smad1/5/8 pathway, but not TGFbeta-mediated reporter gene activity. Biotin labeling of the cell surface proteins followed by their immunoblot revealed that SF3b4 decreased the cell surface BMPRI-A levels. Further analysis by molecular modeling of the intracellular domain of BMPR-IA, coupled with binding studies of its several mutants, indicated that the site(s) for SF3b4 binding is not directly associated with the C-terminal lobe and the activation segment. Taken together, these results suggest that SF3b4, known to be localized in the nucleus and involved in RNA splicing, binds BMPR-IA and specifically inhibits BMP-mediated osteochondral cell differentiation. 相似文献
83.
Shindou H Hishikawa D Nakanishi H Harayama T Ishii S Taguchi R Shimizu T 《The Journal of biological chemistry》2007,282(9):6532-6539
Platelet-activating factor (PAF) is a potent proinflammatory lipid mediator eliciting a variety of cellular functions. Lipid mediators, including PAF are produced from membrane phospholipids by enzymatic cascades. Although a G protein-coupled PAF receptor and degradation enzymes have been cloned and characterized, the PAF biosynthetic enzyme, aceyl-CoA:lyso-PAF acetyltransferase, has not been identified. Here, we cloned lyso-PAF acetyltransferase, which is critical in stimulus-dependent formation of PAF. The enzyme is a 60-kDa microsomal protein with three putative membrane-spanning domains. The enzyme was induced by bacterial endotoxin (lipopolysaccharide), which was suppressed by dexamethasone treatment. Surprisingly, the enzyme catalyzed not only biosynthesis of PAF from lyso-PAF but also incorporation of arachidonoyl-CoA to produce PAF precursor membrane glycerophospholipids (lysophosphatidylcholine acyltransferase activity). Under resting conditions, the enzyme prefers arachidonoyl-CoA and contributes to membrane biogenesis. Upon acute inflammatory stimulation with lipopolysaccharide, the activated enzyme utilizes acetyl-CoA more efficiently and produces PAF. Thus, our findings provide a novel concept that a single enzyme catalyzes membrane biogenesis of inflammatory cells while producing a prophlogistic mediator in response to external stimuli. 相似文献
84.
The anterior cingulate cortex (ACC) is critical for brain functions including learning, memory, fear and pain. Long-term synaptic potentiation (LTP), a cellular model for learning and memory, has been reported in the ACC neurons. Unlike LTP in the hippocampus and amygdala, two key structures for memory and fear, little is known about the synaptic mechanism for the expression of LTP in the ACC. Here we use whole-cell patch clamp recordings to demonstrate that cingulate LTP requires the functional recruitment of GluR1 AMPA receptors; and such events are rapid and completed within 5-10 min after LTP induction. Our results demonstrate that the GluR1 subunit is essential for synaptic plasticity in the ACC and may play critical roles under physiological and pathological conditions. 相似文献
85.
Fukasawa A Nagashima T Aoyama T Fukuda N Matsuda H Ueno T Sugiyama H Nagase H Matsumoto Y 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,859(2):272-275
A simple and sensitive high-performance liquid chromatography (HPLC) method utilizing UV detection was developed for the determination of plasma pyrrole (Py)-imidazole (Im) polyamides in rats and applied to the pharmacokinetic study of compounds. After deproteinization of plasma with methanol, Py-Im polyamides were analyzed with a reversed-phase TSK-GEL ODS-80TM (4.6 mmx15.0 cm TOSOH Co., Japan) column maintained at 40 degrees C. The mobile phase solvent A was 0.1% acetic acid and the solvent B was HPLC-grade acetonitrile (0-10 min, A: 100-20%, B: 0-80% linear gradient; 10-15 min, A: 40%, B: 60%). The flow rate was 1.0 ml/min. The detection wavelength was set at 310 nm. The method was used to determine the plasma concentration time profiles of Py-Im polyamides after intravenous injection. 相似文献
86.
Uchii Kimiko Wakimura Kei Kikko Takeshi Yonekura Ryuji Kawaguchi Riho Komada Honoka Yamanaka Hiroki Kenzaka Takehiko Tani Katsuji 《Limnology》2022,23(1):49-56
Limnology - Gnathopogon caerulescens is an endangered but commercially important fish in Lake Biwa, Japan. The population size of G. caerulescens has drastically reduced in the past decades, and... 相似文献
87.
Akihiro Hirata Yoko Miyamoto Akihisa Kaneko Hiroki Sakai Kyoko Yoshizaki Tokuma Yanai Takako Miyabe‐Nishiwaki Juri Suzuki 《Journal of medical primatology》2019,48(2):137-140
Primary neuroendocrine neoplasm of the liver is extremely rare in both humans and non‐human primates. The present report describes the clinical and pathological findings of an aged Japanese macaque (Macaca fuscata) with hepatic neuroendocrine carcinoma. To our knowledge, this is the first report of hepatic neuroendocrine neoplasm in macaques. 相似文献
88.
Jianlin Han Marion Jean Christian Roussel Hiroki Moriwaki Vadim A. Soloshonok 《Chirality》2019,31(4):328-335
Herein, we disclose the design of a model Ni(II) complex of glycine Schiff base possessing single‐nitrogen stereogenic center, which was successfully used for high‐performance liquid chromatography (HPLC)‐assisted assessment of its configurational stability. The major finding is that the configurational stability of the Ni(II)‐coordinated nitrogen is profoundly dependent on the reaction conditions used, in particular the solvent, and can range from inconsequential (t½ less than 5 min) to virtually completely stable (t½ 90 y). The discovery reported in this study most likely to be of certain theoretical and synthetic value. 相似文献
89.
90.
Keiichi Hata Naohiro Kobayashi Keita Sugimura Weihua Qin Deis Haxholli Yoshie Chiba Sae Yoshimi Gosuke Hayashi Hiroki Onoda Takahisa Ikegami Christopher
B Mulholland Atsuya Nishiyama Makoto Nakanishi Heinrich Leonhardt Tsuyoshi Konuma Kyohei Arita 《Nucleic acids research》2022,50(21):12527
Ubiquitin-like with PHD and RING finger domain-containing protein 1 (UHRF1)-dependent DNA methylation is essential for maintaining cell fate during cell proliferation. Developmental pluripotency-associated 3 (DPPA3) is an intrinsically disordered protein that specifically interacts with UHRF1 and promotes passive DNA demethylation by inhibiting UHRF1 chromatin localization. However, the molecular basis of how DPPA3 interacts with and inhibits UHRF1 remains unclear. We aimed to determine the structure of the mouse UHRF1 plant homeodomain (PHD) complexed with DPPA3 using nuclear magnetic resonance. Induced α-helices in DPPA3 upon binding of UHRF1 PHD contribute to stable complex formation with multifaceted interactions, unlike canonical ligand proteins of the PHD domain. Mutations in the binding interface and unfolding of the DPPA3 helical structure inhibited binding to UHRF1 and its chromatin localization. Our results provide structural insights into the mechanism and specificity underlying the inhibition of UHRF1 by DPPA3. 相似文献