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81.
Yusuke Sekiguchi Tetsuko Nakaniwa Takayoshi Kinoshita Isao Nakanishi Kazuo Kitaura Akira Hirasawa Gozoh Tsujimoto Toshiji Tada 《Bioorganic & medicinal chemistry letters》2009,19(11):2920-2923
We determined the 2.35-Å crystal structure of a human CK2 catalytic subunit (referred to as CK2α complexed with the ATP-competitive, potent CK2 inhibitor ellagic acid. The inhibitor binds to CK2α with a novel binding mode, including water-mediated hydrogen bonds. This structural information may support discovery of potent CK2 inhibitors. 相似文献
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Acute and fulminant liver failure induced by viral hepatitis, alcohol or other hepatotoxic drugs are associated with tumor necrosis factor (TNF) production. D-Galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure. In this model, TNF-alpha plays a central role in the pathogenesis of D-GalN/LPS-induced liver injury in mice. Y-40138, N-[1-(4-[4-(pyrimidin-2-yl)piperazin-1-yl]methyl phenyl)cyclopropyl] acetamide.HCl inhibits TNF-alpha and augments interleukin (IL)-10 production in LPS-injected mice in plasma. In the present study, we examined the effect of Y-40138 on D-GalN/LPS-induced hepatitis. Y-40138 (10mg/kg, i.v.) significantly suppressed TNF-alpha and monocyte chemoattractant protein-1 (MCP-1) production and augmented IL-10 production in plasma. In addition, Y-40138 significantly inhibited TNF-alpha production induced by direct interaction between human T lymphocytes and macrophages. Y-40138 suppressed plasma alanine transaminase (ALT) elevation and improved survival rate in D-GalN/LPS-injected mice, and it is suggested that the protective effect of Y-40138 on hepatitis may be mediated by inhibition of TNF-alpha and MCP-1, and/or augmentation of IL-10. This compound is expected to be a new candidate for treatment of cytokine and/or chemokine-related liver diseases such as alcoholic hepatitis. 相似文献
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86.
Microtubular elements in the chloroplasts (chl-MTs) of Oedogonium capilliforme Wittrock were examined by conventional electron microscopy and immunoelectron microscopy. Chl-MTs were frequently seen in the terminal, convex, and concave peripheral regions of the chloroplasts. Each bundle of chl-MTs was composed of 2–25 tubular elements. Some chl-MTs were located in the stroma. Chl-MTs frequently bridged two areas of the envelope membrane near the apex of convex regions of chloroplasts. Some chl-MTs were closely associated with the envelope membrane via apparent anchors along their length. The distribution patterns of chl-MTs and their appearance suggest that chl-MTs are involved in the maintenance of the outer shape of chloroplasts. However, immunoelectron microscopy with an antibody against α-tubulin indicated that the chl-MTs are not composed of tubulin. 相似文献
87.
Formation of Chlorophyll-Protein Complexes during Greening 1. Distribution of Newly Synthesized Chlorophyll among Apoproteins 总被引:1,自引:0,他引:1
Shimada Yukihisa; Tanaka Ayumi; Tanaka Yoshito; Takabe Tetsuko; Takabe Teruhiro; Tsuji Hideo 《Plant & cell physiology》1990,31(5):639-647
The relationship between the accumulation of Chl and the apoproteinsof the light-harvesting Chl a/b-protein complex of PS II (LHCII)during the greening of cucumber cotyledons was studied. LHCIIapoproteins were not detected in etiolated cotyledons. Uponillumination, Chl a was formed as a result of photoconversionof protochlorophyllide (Pchlide) which had accumulated in thedark. During the lag period that preceded the accumulation ofChl, a small amount of LHCII apoproteins appeared. The amountof LHCII apoproteins increased with increases in levels of Chlb, though somewhat more rapidly during the first 10 h of greening.Treatment with benzyladenine (BA) or levulinic acid (LA) wasused to vary the supply of Chl a for apoproteins by promotingor inhibiting the synthesis of Chl a, respectively. LA decreasedbut BA increased the rate of accumulation of Chl b and LHCIIapoproteins. Only small amounts of Chl b and LHCII apoproteinswere formed under intermittent illumination. However, in thepresence of chloramphenicol (CAP), which inhibits the synthesisof plastome-coded proteins including apoproteins of the P700-Chla-protein complex (CP1) and a Chl a-protein complex of PS II(CPa), we observed the accumulation of Chl b and LHCII apoproteins,both of which are of nuclear origin. During incubation in thedark after intermittent exposure to light, CAP alone allowedneither destruction nor accumulation of Chl b and LHCII apoproteins,but it did enhance the effect of CaCl2 in inducing both Chlb and these apoproteins. These results can be explained by assumingthat apoproteins of CP1 and CPa have a higher affinity for Chla than do LHCII apoproteins. When the availability of Chl ais limited, these apoproteins compete with one another for Chla, with the resultant preferential formation of CP1 and CPa.However, when the supply of Chl a becomes large enough for saturationof apoproteins of CP1 and CPa, some of the Chl a is incorporatedinto LHCII apoproteins either directly or after conversion toChl b. Thus, the formation of different Chl-protein complexes(CPs) is regulated by the relative rates of synthesis of Chla and apoproteins and by differential affinities of the apoproteinsfor Chl a.
4Present address: Kyowa Hakko Co., Ltd., 4041, Ami-machi, Inashiki,Ibaraki, 300-03 Japan (Received September 14, 1989; Accepted April 26, 1990) 相似文献
88.
The effects of mouse epidermal growth factor (mEGF) on the hypothalamic-pituitary-adrenocortical axis were studied in vivo in conscious male rats and in vitro with cultured anterior pituitary cells. Both intravenous (i.v.) and intracerebroventricular (i.c.v.) injections of mEGF (5-20 ng: 8.3-33.3 pmol) produced significant, dose-related increases in plasma ACTH and corticosterone concentrations. The potency of mEGF is 1/20-1/50 of that of rat corticotropin-releasing factor (rCRF), and pretreatment with 150 micrograms alpha-helical CRF (9-41) completely abolished the effects of the two peptides. mEGF in concentrations ranging from 10 pM to 10 nM did not significantly affect ACTH release from dispersed anterior pituitary cells. It also failed to alter ACTH secretion in response to rCRF. These results indicate that mEGF stimulates the pituitary-adrenocortical axis through a CRF-dependent mechanism. 相似文献
89.
Kaori Taniguchi Mariko Funasaki Akio Kishida Samir K. Sadhu Firoj Ahmed Masami Ishibashi Ayumi Ohsaki 《Bioorganic & medicinal chemistry letters》2018,28(6):1063-1066
Two new coumarins (1, 2) and a new xanthone (3), together with 14 known compounds—eight coumarins (4, 5, 9, 10, 12–15), three xanthones (11, 16, 17), a benzoic acid (6) and two flavonones (7, 8)—were isolated from the leaves of Rhizophora mucronata. The structures of the compounds were elucidated by spectroscopic (IR, MS, and NMR) analyses. The isolated compounds were tested for cytotoxicity against human cancer cell lines HL-60 and HeLa. Among these compounds, only compound 16 inhibited the growth of both HeLa (IC50?=?4.8?μM) and HL-60 (IC50?=?1.0?μM) cells. Compounds 4, 7, 10, and 12 exhibited moderate activity against HeLa cells (IC50?=?3.8–8.3?μM). Compounds 5, 9, 11, and 17 showed moderate activity against HL-60 cells (IC50?=?2.2–6.3?μM). Higher selectivity against HL-60 cell lines was observed for compounds 5, 9, 11, and 16 with SI values (NIH 3T3/HL-60) of 8.6, 19.2, 9.4, and 10.2, respectively. 相似文献
90.
Kanae Nakamura Tsunao Kishida Akika Ejima Riho Tateyama Satoru Morishita Tomoji Ono Michiaki Murakoshi Keikichi Sugiyama Hoyoku Nishino Osam Mazda 《Biometals》2018,31(3):415-424
Lactoferrin (LF) is a multifunctional protein in mammalian milk. We previously reported that enteric-coated bovine LF reduced the visceral fat in a double-blind clinical study. We further demonstrated that bovine LF (bLF) inhibited adipogenesis and promoted lipolysis in white adipocytes, but the effect of bLF on brown adipocytes has not been clarified. In this study, we investigated the effects of bLF on energy expenditure and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway using human reprogrammed brown adipocytes generated by gene transduction. bLF at concentrations of ≥?100 μg/mL significantly increased uncoupling protein 1 (UCP1) mRNA levels, with the maximum value observed 4 h after bLF addition. At the same time point, bLF stimulation also significantly increased oxygen consumption. Signaling pathway analysis revealed rapid increases of intracellular cAMP and cAMP response element-binding protein (CREB) phosphorylation levels beginning 5 min after bLF addition. The mRNA levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were also significantly increased after 1 h of bLF stimulation. H-89, a specific PKA inhibitor, abrogated bLF-induced UCP1 gene expression. Moreover, receptor-associated protein (Rap), an antagonist of low-density lipoprotein receptor-related protein 1 (LRP1), significantly reduced bLF-induced UCP1 gene expression in a dose-dependent manner. These results suggest that bLF promotes UCP1 gene expression in brown adipocytes through the cAMP-PKA signaling pathway via the LRP1 receptor, leading to increased energy expenditure. 相似文献