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101.
Ismiarni Komala Takuya Ito Fumihiro Nagashima Yasuyuki Yagi Masatoshi Kawahata Kentaro Yamaguchi Yoshinori Asakawa 《Phytochemistry》2010,71(11-12):1387-1394
Cembrane-type diterpenoids, 13,18,20-epi-iso-chandonanthone (1) and (8E)-4α-acetoxy-12α,13α-epoxycembra-1(15),8-diene (2), two fusicoccane-type diterpenoids, fusicoauritone 6α-methyl ether (3) and 6β,10β-epoxy-5β-hydroxyfusicocc-2-ene (4) and a zierane sesquiterpene γ-lactone, chandolide (5) were isolated from the Tahitian liverwort Chandonanthus hirtellus (Web.) Mitt., together with eight known diterpenoids, chandonanthine (6), fusicogigantone A (7), fusicogigantone B (8), fusicogigantepoxide (9), anadensin (10), fusicoauritone (11), ent-verticillol (12) and ent-epi-verticillol (13). Their structures were established by a combination of extensive NMR spectroscopy and/or X-ray crystallographic analyses. Compounds 1, 5 and 10 showed weak cytotoxic activity against HL-60. Compound 3 also indicated weak cytotoxic activity against KB cell lines. 相似文献
102.
Tatsutoshi Inuzuka Hironori Suzuki Masato Kawasaki Hideki Shibata Soichi Wakatsuki Masatoshi Maki 《BMC structural biology》2010,10(1):25
Background
ALG-2 (a gene product of PDCD6) belongs to the penta-EF-hand (PEF) protein family and Ca2+-dependently interacts with various intracellular proteins including mammalian Alix, an adaptor protein in the ESCRT system. Our previous X-ray crystal structural analyses revealed that binding of Ca2+ to EF3 enables the side chain of R125 to move enough to make a primary hydrophobic pocket (Pocket 1) accessible to a short fragment of Alix. The side chain of F122, facing a secondary hydrophobic pocket (Pocket 2), interacts with the Alix peptide. An alternatively spliced shorter isoform, designated ALG-2ΔGF122, lacks Gly121Phe122 and does not bind Alix, but the structural basis of the incompetence has remained to be elucidated. 相似文献103.
Yosuke Ichijima Ken-ichi Yoshioka Yoshiko Yoshioka Keitaro Shinohe Hiroaki Fujimori Junya Unno Masatoshi Takagi Hidemasa Goto Masaki Inagaki Shuki Mizutani Hirobumi Teraoka 《PloS one》2010,5(1)
During tumorigenesis, cells acquire immortality in association with the
development of genomic instability. However, it is still elusive how genomic
instability spontaneously generates during the process of tumorigenesis. Here,
we show that precancerous DNA lesions induced by oncogene acceleration, which
induce situations identical to the initial stages of cancer development, trigger
tetraploidy/aneuploidy generation in association with mitotic aberration.
Although oncogene acceleration primarily induces DNA replication stress and the
resulting lesions in the S phase, these lesions are carried over into the M
phase and cause cytokinesis failure and genomic instability. Unlike directly
induced DNA double-strand breaks, DNA replication stress-associated lesions are
cryptogenic and pass through cell-cycle checkpoints due to limited and
ineffective activation of checkpoint factors. Furthermore, since damaged M-phase
cells still progress in mitotic steps, these cells result in chromosomal
mis-segregation, cytokinesis failure and the resulting tetraploidy generation.
Thus, our results reveal a process of genomic instability generation triggered
by precancerous DNA replication stress. 相似文献
104.
Unlike known Chlamydomonas species, Chlamydomonas sp. strain W80, which was isolated from seawater, shows tolerance to salt and cadmium. In this study, we purified and characterized cysteine protease from Chlamydomonas sp. strain W80 cells and also investigated their response to oxidative stress. The protease was purified 2760-fold with a yield of 2.6% by five steps of successive chromatography. This protease had a pH optimum of 8.0 and was specific only for tert -butoxycarbonyl (Boc)-Leu-Arg-Arg-4-methylcoumaryl-7-amide (MCA) (Boc-LRR-MCA) and Boc-Val-Leu-Lys-MCA as substrates among eight fluorogenic peptides tested. The K m value was estimated to be 44.4 μ M for Boc-LRR-MCA. The molecular weight of the protease was determined to be approximately 102 kDa by Superdex 200 gel filtration and 60 kDa by SDS–PAGE, suggesting that this enzyme is a dimer. This enzyme was inhibited by the cysteine protease inhibitors leupeptin and N-ethylmaleimide but neither inhibited by phenylmethylsulfonyl fluoride or ethylenediaminetetraacetic acid nor activated by metal cations. These findings indicate that this enzyme is likely a cysteine protease. When strain W80 was grown under oxidative stress in the presence of methyl viologen and cadmium chloride, cysteine protease activity was about 30–90% higher than normal, whereas no changes were observed in carbon enrichment or senescence. It is likely that this protease is upregulated in response to oxidative stress and plays a role in the maintenance of cell metabolism under oxidative stress conditions. 相似文献
105.
Dihydrosphingosine C4 hydroxylase is a key enzyme in the biosynthesis of phytosphingosine, a major constituent of sphingolipids in plants and yeasts. The rice genome contains five homologue genes for dihydrosphingosine C4 hydroxylase, DSH1-DSH5, whose gene products show high degrees of homology to the yeast counterpart, SUR2. Among them, expression of DSH1, DSH2 and DSH4 was detected, and DSH1 and DSH4 complement the yeast sur2 mutation. The DSH1 gene was specifically and abundantly expressed in vascular bundles and apical meristems. In particular, very strong expression was detected in the stigmas of flowers. Repression of DSH1 expression by the antisense gene or RNA interference (RNAi) resulted in a severe reduction of fertility. In the transformants in which DSH1 expression was suppressed, significantly increased expression of DSH2 was found in leaves but not in pistils, suggesting that there was tissue-specific correlation between DSH1 and DSH2 expression. Our results indicate that the product of DSH1 may be involved in plant viability or reproductive processes, and that the phenotype of sterility is apparently caused by loss of function of DSH1 in the stigma. It is also suggested that there is a complex mechanism controlling the tissue-specific expression of the DSH1 gene. 相似文献
106.
107.
IL-28 elicits antitumor responses against murine fibrosarcoma 总被引:3,自引:0,他引:3
Numasaki M Tagawa M Iwata F Suzuki T Nakamura A Okada M Iwakura Y Aiba S Yamaya M 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(8):5086-5098
IL-28 is a recently described antiviral cytokine. In this study, we investigated the biological effects of IL-28 on tumor growth to evaluate its antitumor activity. IL-28 or retroviral transduction of the IL-28 gene into MCA205 cells did not affect in vitro growth, whereas in vivo growth of MCA205IL-28 was markedly suppressed along with survival advantages when compared with that of controls. When the metastatic ability of IL-28-secreting MCA205 cells was compared with that of controls, the expression of IL-28 resulted in a potent inhibition of metastases formation in the lungs. IL-28-mediated suppression of tumor growth was mostly abolished in irradiated mice, indicating that irradiation-sensitive cells, presumably immune cells, are primarily involved in the IL-28-induced suppression of tumor growth. In vivo cell depletion experiments displayed that polymorphonuclear neutrophils, NK cells, and CD8 T cells, but not CD4 T cells, play an equal role in the IL-28-mediated inhibition of in vivo tumor growth. Consistent with these findings, inoculation of MCA205IL-28 into mice evoked enhanced IFN-gamma production and cytotoxic T cell activity in spleen cells. Antitumor action of IL-28 is partially dependent on IFN-gamma and is independent of IL-12, IL-17, and IL-23. IL-28 increased the total number of splenic NK cells in SCID mice and enhanced IL-12-induced IFN-gamma production in vivo and expanded spleen cells in C57BL/6 mice. Moreover, IL-12 augmented IL-28-mediated antitumor activity in the presence or absence of IFN-gamma. These findings indicate that IL-28 has bioactivities that induce innate and adaptive immune responses against tumors. 相似文献
108.
109.
110.
The extracellular matrix (ECM) acts as a critical factor during morphogenesis. Because the organization of the ECM directly
influences the structure of tissues and organs, a determination of the way that ECM organization is regulated should help
to clarify morphogenesis. We have analyzed the assembly of Del1, an ECM protein produced by endothelial cells in embryos,
in the ECM. Del1 consists of three epidermal growth factor repeats (E1–E3) at its N-terminus and two discoidin domains (C1,
C2) at its C-terminus. Experiments with various deletion mutants of Del1 have revealed that fragments containing the C-terminus
of C1, which has a lectin-like structure, direct deposition in the ECM. The efficiency of deposition varies according to the
presence of other domains in Del1. A fragment containing E3 and C1 has the strongest deposition activity, whereas fragments
containing C2, which is highly homologous to C1, have low deposition activity. Digestion of ECM with hyaluronidase from bovine
testis releases Del1 from the ECM, suggesting that glycosaminoglycans are involved in the deposition of Del1. In vivo gene
transfer experiments have shown that fusion with the deposition domain of Del1 dramatically alters the distribution of exogenous
proteins in mice. Thus, the extent of Del1 deposition may modify the organization of the ECM. 相似文献