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21.
22.
Yoshiro Kinoshita Michinori Misaka Shuhei Kubota Hisao Ishikawa 《Bioscience, biotechnology, and biochemistry》2013,77(11):1975-1981
A mixture of two thionocarbamates was subjected to the acid-catalyzed rearrangement. A sample of the reaction mixture was analyzed by glpc and resolved into four components. From the cross-over result, it has been concluded that the acid-catalyzed rearrangement of alkyl thionocarbamates into the isomeric thiolcarbamates proceeds by an intermolecular alkylating mechanism. This conclusion was supported by the detection of a transalkylated intermediate. 相似文献
23.
An anticomplementary agent, K-76 monocarboxylic acid: its site and mechanism of inhibition of the complement activation cascade. 总被引:11,自引:0,他引:11
K Hong T Kinoshita W Miyazaki T Izawa K Inoue 《Journal of immunology (Baltimore, Md. : 1950)》1979,122(6):2418-2423
A monocarboxylic acid derivative (K-76 COOH) of K-76, purified from the culture filtrate of Stachybotrys complement I nov. sp. K-76, inhibits complement (C) activity. Its inhibitory action is mainly on C5 step. It strongly inhibits the generation of EAC1,4b,2a,3b,5b from C5 and EAC1,4b,2a,3b, and accelerates the decay of EAC1,4b,2a,3b,5b. It also causes some inhibition of the reactions of the reactions of C2,C3,C6,C7 and C9 with their respective preceding intermediate cells. It has no effect on the generation of EAC1,4b from C4 and EAC1, or of EAC-8 from C8 and EAC-7, and apparently increases the generation of EAC1,4b from C1 and EAC4b probably by inhibiting transfer or turnover of C1. It does not affect the rate of decay of EAC1,4b,2a or the T max of generation of EAC1,4b,2a, and it inhibits immune adherence only at high concentration. K-76 COOH also strongly inhibits hemolysis through the alternative pathway of C activation by cobra venom factor, but it does not seem to inhibit the early steps of the alternative pathway, because it has little affect on the consumption of C3 or the conversion of beta 1C to beta 1A on treatment of C serum with zymosan. K-76 COOH probably combines with C5 molecules, forming the inactive complexes, or it causes the structural alteration of C5. 相似文献
24.
Cell proliferation was examined in the back and tail epidermis of larval Xenopus laevis using bromodeoxyuridine (BrdU). The BrdU labeling index of the back epidermis increased temporally at stage 59, followed by a rapid decrease to the same level as at stage 51. The temporal increase in cell proliferation of the back epidermis produced a new epidermal layer composed of basal cells. In vitro analysis showed that tri-iodothyronine (T3) promotes cell proliferation of basal cells but suppresses that of skein cells. Immunohistochemical studies showed that the newly formed basal cell layer functions as adult precursor cells which produce the adult epidermal cells. In contrast to the back epidermis, the labeling index of the tail epidermis decreased from stage 57. However, when the tail skin was transplanted to the back area, cell proliferation in the tail epidermis increased to the same level as that of the normal back epidermis. Cell proliferation of the back epidermis was not suppressed by transplanting the skin to the tail area. These results suggest that some promoting factors are produced in the body region and regulate the number of adult precursor cells, which determine the developmental fate of the larval skin. 相似文献
25.
26.
Masaki Asada Tetsuo Obitsu Atsushi Kinoshita Yoshihiko Nakai Toshihiko Nagase Isamu Sugimoto Motoyuki Tanaka Hiroya Takizawa Ken Yoshikawa Kazutoyo Sato Masami Narita Shuichi Ohuchida Hisao Nakai Masaaki Toda 《Bioorganic & medicinal chemistry letters》2010,20(8):2639-2643
A series of novel N-acylsulfonamide analogs were synthesized and evaluated for their binding affinity and antagonist activity for the EP3 receptor subtype. Representative compounds were also evaluated for their inhibitory effect on PGE2-induced uterine contraction in pregnant rats. Among those tested, a series of N-acylbenzenesulfonamide analogs were found to be more potent than the corresponding carboxylic acid analogs in both the in vitro and in vivo evaluations. The structure activity relationships (SAR) are also discussed. 相似文献
27.
Using single-molecule force spectroscopy to probe ICAM-1 interactions with recombinant αLβ2 immobilized on microspheres and β2 integrin on neutrophils, we quantified an impressive hierarchy of long-lived, high-strength states of the integrin bond, which start from basal levels with activation in solutions of divalent cations and shift dramatically upward to hyperactivated states with cell signaling. Taking advantage of very rare events, we used repeated measurements of bond lifetimes under steady ramps of force to achieve a direct assay for the off-rates of ICAM-1 from β2 integrin throughout the course of each experiment. In our companion article I, we demonstrate the assay using results from tests of a monovalent ICAM-1 probe against recombinant αLβ2 on microspheres in millimolar solutions of divalent cations (Ca2+, Mg2+, Mn2+). In this article, we examine the impact of inside-out and outside-in signaling in neutrophils on the lifetimes and mechanical strengths of ICAM-1 bonds to β2 integrin on the cell surface. Even though ICAM-1 bonds to recombinant αLβ2 on microspheres in Mg2+ or Mn2+ can live for long periods of time under slow pulling, here we show that stimulation of neutrophils in Mg2+ plus the chemokine IL-8 (i.e., inside-out signaling) induces several-hundred-fold longer lifetimes for ICAM-1 attachments to LFA-1, creating strong bonds at very slow pulling speeds where none are perceived in Mg2+ or Mn2+ alone. Similar changes are observed with outside-in signaling, i.e., long lifetimes and increased bond strength also occur when neutrophils are bound with the activating (anti-CD18) monoclonal 240Q. Limiting our investigation to rare events using very dilute ICAM-1 probes, we show that although the prolonged lifetimes of cell surface attachments for both inside-out and outside-in signaling exhibit single-bond-like statistics for dissociation under force, they are consistent with a tightly coupled dimeric ICAM-1 interaction with a pair of LFA-1 heterodimers. 相似文献
28.
Saurabh Sahar Loredana Zocchi Chisato Kinoshita Emiliana Borrelli Paolo Sassone-Corsi 《PloS one》2010,5(1)
Background
Circadian rhythms govern a large array of physiological and metabolic functions. To achieve plasticity in circadian regulation, proteins constituting the molecular clock machinery undergo various post-translational modifications (PTMs), which influence their activity and intracellular localization. The core clock protein BMAL1 undergoes several PTMs. Here we report that the Akt-GSK3β signaling pathway regulates BMAL1 protein stability and activity.Principal Findings
GSK3β phosphorylates BMAL1 specifically on Ser 17 and Thr 21 and primes it for ubiquitylation. In the absence of GSK3β-mediated phosphorylation, BMAL1 becomes stabilized and BMAL1 dependent circadian gene expression is dampened. Dopamine D2 receptor mediated signaling, known to control the Akt-GSK3β pathway, influences BMAL1 stability and in vivo circadian gene expression in striatal neurons.Conclusions
These findings uncover a previously unknown mechanism of circadian clock control. The GSK3β kinase phosphorylates BMAL1, an event that controls the stability of the protein and the amplitude of circadian oscillation. BMAL1 phosphorylation appears to be an important regulatory step in maintaining the robustness of the circadian clock. 相似文献29.
The thermal stability of formaldehyde dehydrogenase (FaDH) from Pseudomonas sp. was examined and controlled by encapsulation in liposomes with β-reduced nicotinamide adenine dinucleotide (NADH). The activity of 4.8 μg/mL free FaDH at pH 8.5 in catalyzing the oxidation of 50 mM formaldehyde was highly dependent on temperature so that the activity at 60 °C was 27 times larger than that at 25 °C. Thermal stability of the FaDH activity was examined with and without liposomes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Rapid deactivation of free FaDH was observed at 60 °C because of its dissociation into two subunits. The rate of dissociative deactivation of POPC liposome-encapsulated FaDH was smaller than that of the free enzyme. The liposomal FaDH was however progressively deactivated for the incubation period of 60 min eventually leading to complete loss of its activity. The free FaDH and NADH molecules were revealed to form the thermostable binary complex. The thermal stability of POPC liposome-encapsulated FaDH and NADH system was significantly higher than the liposomal enzyme without cofactor. The above results clearly show that NADH is a key molecule that controls the activity and stability of FaDH in liposomes at high temperatures. 相似文献
30.
Tsutsumi YM Tsutsumi R Mawatari K Nakaya Y Kinoshita M Tanaka K Oshita S 《Life sciences》2011,88(15-16):725-729
AimsCompound K (C-K; 20-O-d-glucopyranosyl-20(S)-protopanaxadiol) is a novel ginsenoside metabolite formed by intestinal bacteria and does not occur naturally in ginseng. In this study, we investigated whether administration of C-K has protective effects on myocardial ischemia-reperfusion injury and its potential mechanisms.Main methodsWe used in vivo mouse models of ischemia-reperfusion injury and performed biochemical assays in excised hearts.Key findingsC-K reduced infarct size compared with the control group after ischemia-reperfusion. Immunoblot analysis showed that C-K significantly enhanced protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) activity. Wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked cardiac protection in vivo and attenuated phosphorylation of Akt and eNOS. Additionally, the hearts of C-K pretreated mice showed inhibition of mitochondrial swelling induced by Ca2+.SignificanceThis study showed that Compound K pretreatment has protective effects on myocardial ischemia-reperfusion injury, partly by mediating the activation of PI3K pathway and phosphorylation of Akt and eNOS. 相似文献