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991.
992.
Induction of poly(ADP-ribose) polymerase gene expression in lectin-stimulated human T lymphocytes is dependent on protein synthesis 总被引:1,自引:0,他引:1
M Menegazzi F Gerosa M Tommasi K Uchida M Miwa T Sugimura H Suzuki F Gelosa 《Biochemical and biophysical research communications》1988,156(2):995-999
The poly(ADP-ribose) polymerase mRNA level in quiescent T lymphocytes was low, but was significantly higher than that in B lymphocytes or monocytes. When T lymphocytes were stimulated with phytohemagglutinin, a prompt increase in the mRNA level was observed from 4 hours after stimulation. The level of poly(ADP-ribose) polymerase mRNA reached a maximum in the late G1 phase about 1-2 days after lectin stimulation, and then decreased gradually returning to the basal level 10 days after lectin stimulation. Cycloheximide abrogated increase in poly(ADP-ribose) polymerase gene expression suggesting that a newly synthesized protein(s) was involved in poly(ADP-ribose) polymerase gene induction in lectin-stimulated T lymphocytes. 相似文献
993.
K Ogita A Ohkawara T Suzuki T Ohgaki S Uchida H Meguri Y Yoneda 《Neurochemistry international》1992,21(1):135-147
The effects of a cerebral anti-ischemic drug ifenprodil on the receptor ionophore complex of an N-methyl-D-aspartate (NMDA)-sensitive subclass of central excitatory amino acid receptors were examined using [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10- imine (MK-801) binding in rat brain synaptic membrane preparations as a biochemical measure. The binding in membrane preparations not extensively washed was markedly inhibited not only by competitive NMDA antagonists such as (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic, D-2-amino-5-phosphonovaleric and D-2-amino-7-phosphonoheptanoic acids, but also by competitive antagonists at the strychnine-insensitive glycine (Gly) site including 7-chlorokynurenic acid and 6,7-dichloroquinoxaline-2,3-dione. Among several proposed ligands for alpha-adrenergic receptors tested, ifenprodil most potently inhibited the binding in these membrane preparations due to a decrease in the density of the binding sites without significantly affecting the affinity. Ifenprodil also inhibited the binding of [3H]N-[1-(2-thienyl)cyclohexyl]piperidine as well as of [3H]MK-801 to open NMDA channels in a concentration-dependent manner at concentrations above 10 nM in membrane preparations extensively washed but not treated by a detergent, with a Hill coefficient of less than unity. Further treatment of extensively washed membrane preparations with a low concentration of Triton X-100 resulted in an almost complete abolition of [3H]MK-801 binding, and the binding was restored to the level found in membrane preparations not extensively washed following the addition of both L-glutamic acid (Glu) and Gly. Ifenprodil was effective in inhibiting [3H]MK-801 binding via reducing both initial association and dissociation rates in Triton-treated membrane preparations, irrespective of the presence of Glu and Gly added. The binding in Triton-treated membrane preparations was additionally potentiated by the polyamine spermidine in a concentration-dependent manner at concentrations above 10 microM in the presence of both Glu and Gly at maximally effective concentrations. Ifenprodil invariably diminished the abilities of these three stimulants to potentiate [3H]MK-801 binding at concentrations over 1 microM in a manner that the maximal responses each were reduced. These results suggest that ifenprodil does not interfere with the NMDA receptor complex as a specific isosteric antagonist at the polyamine domain in contrast to the prevailing view. 相似文献
994.
Yukiko Ihara Yuko Tomonoh Masanobu Deshimaru Bo Zhang Taku Uchida Atsushi Ishii Shinichi Hirose 《PloS one》2016,11(2)
The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG), a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB), which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+) bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT) littermates, at 63–100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg) were recorded using a video-electroencephalography (EEG) monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine’s scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations. 相似文献
995.
996.
Kazuhiko S.K. Uchida Kentaro Takagaki Kazuki Kumada Youko Hirayama Tetsuo Noda Toru Hirota 《The Journal of cell biology》2009,184(3):383-390
The spindle assembly checkpoint (SAC) monitors the attachment of microtubules to the kinetochore and inhibits anaphase when microtubule binding is incomplete. The SAC might also respond to tension; however, how cells can sense tension and whether its detection is important to satisfy the SAC remain controversial. We generated a HeLa cell line in which two components of the kinetochore, centromere protein A and Mis12, are labeled with green and red fluorophores, respectively. Live cell imaging of these cells reveals repetitive cycles of kinetochore extension and recoiling after biorientation. Under conditions in which kinetochore stretching is suppressed, cells fail to silence the SAC and enter anaphase after a delay, regardless of centromere stretching. Monitoring cyclin B levels as a readout for anaphase-promoting complex/cyclosome activity, we find that suppression of kinetochore stretching delays and decelerates cyclin B degradation. These observations suggest that the SAC monitors stretching of kinetochores rather than centromeres and that kinetochore stretching promotes silencing of the SAC signal. 相似文献
997.
Kazuo Matsumoto Shuji Uchida Hiroshi Higuchi Atsushi Mizushima Hiroshi Yoshida 《Life sciences》1983,33(10):963-970
Urea-treatment of the microsome fraction of the heart of guinea-pigs caused selective reduction in the apparent affinity of an agonist (carbachol), but not an antagonist (atropine), to muscarinic acetylcholine receptors (mAChR), measured as inhibition of binding of 3H-quinuclidinyl benzilate (3H-QNB). This effect was similar to that of Gpp(NH)p. The effects of urea-treatment and Gpp(NH)p were not additive. On the other hand, treatment of the microsome fraction with 5,5′-dithiobis (2-nitrobenzoic acid) (DTNB) increased the apparent affinity of agonist, but not antagonist. The effect of DTNB predominated over those of urea-treatment and Gpp(NH)p, when these treatments were combined with DTNB. 相似文献
998.
Shigemitsu Kudou Yvette Fleury Dieter Welti Daniele Magnolato Teiji Uchida Keisuke Kitamura 《Bioscience, biotechnology, and biochemistry》2013,77(9):2227-2233
The isoflavone constituents in soybean seeds were investigated, and 9 kinds of isoflavone glycosides were isolated from the hypocotyls of soybean seeds. Three kinds were proved to be malonylated soybean isoflavones named 6″-O-malonyldaidzin, 6″-O-malonylglycitin and 6″-O-malonylgenistin by UV, MS, IR and NMR. The malonylated isoflavone glycosides as major isoflavone constituents in soybean seed were thermally unstable, and were converted into their corresponding isoflavone glycosides. All of the isoflavone components produced intensely undesirable taste effects such as bitter, astringent and dry mouth feeling. 相似文献
999.
Satoshi Uchida Keiji Itaka Hirokuni Uchida Kentaro Hayakawa Toru Ogata Takehiko Ishii Shigeto Fukushima Kensuke Osada Kazunori Kataoka 《PloS one》2013,8(2)
Messenger RNA (mRNA) introduction is a promising approach to produce therapeutic proteins and peptides without any risk of insertion mutagenesis into the host genome. However, it is difficult to introduce mRNA in vivo mainly because of the instability of mRNA under physiological conditions and its strong immunogenicity through the recognition by Toll-like receptors (TLRs). We used a novel carrier based on self-assembly of a polyethylene glycol (PEG)-polyamino acid block copolymer, polyplex nanomicelle, to administer mRNA into the central nervous system (CNS). The nanomicelle with 50 nm in diameter has a core-shell structure with mRNA-containing inner core surrounded by PEG layer, providing the high stability and stealth property to the nanomicelle. The functional polyamino acids possessing the capacity of pH-responsive membrane destabilization allows smooth endosomal escape of the nanomicelle into the cytoplasm. After introduction into CNS, the nanomicelle successfully provided the sustained protein expression in the cerebrospinal fluid for almost a week. Immune responses after mRNA administration into CNS were effectively suppressed by the use of the nanomicelle compared with naked mRNA introduction. In vitro analyses using specific TLR-expressing HEK293 cells confirmed that the nanomicelle inclusion prevented mRNA from the recognition by TLRs. Thus, the polyplex nanomicelle is a promising system that simultaneously resolved the two major problems of in vivo mRNA introduction, the instability and immunogenicity, opening the door to various new therapeutic strategies using mRNA. 相似文献
1000.