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61.
62.
The Senescence-accelerated Mouse (SAM): A Higher Oxidative Stress and Age-dependent Degenerative Diseases Model 总被引:1,自引:0,他引:1
Chiba Y Shimada A Kumagai N Yoshikawa K Ishii S Furukawa A Takei S Sakura M Kawamura N Hosokawa M 《Neurochemical research》2009,34(4):679-687
The SAM strain of mice is actually a group of related inbred strains consisting of a series of SAMP (accelerated senescence-prone)
and SAMR (accelerated senescence-resistant) strains. Compared with the SAMR strains, the SAMP strains show a more accelerated
senescence process, a shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes
similar to human geriatric disorders. The higher oxidative stress status observed in SAMP mice is partly caused by mitochondrial
dysfunction, and may be a cause of this senescence acceleration and age-dependent alterations in cell structure and function.
Based on our recent observations, we discuss a possible mechanism for mitochondrial dysfunction resulting in the excessive
production of reactive oxygen species, and a role for the hyperoxidative stress status in neurodegeneration in SAMP mice.
These SAM strains can serve as a useful tool to understand the cellular mechanisms of age-dependent degeneration, and to develop
clinical interventions.
Special issue article in honor of Dr. Akitane Mori. 相似文献
63.
Ayako Ueki Yukiko Fukushima Tetsuo Kimoto 《Virchows Archiv. B, Cell pathology including molecular pathology》1976,22(1):315-321
The presence of C3 receptor sites on the cell surfaces of WI-38 fibroblasts was reported in a previous paper. Here the effect of dexamethasone
sodium sulfate of C3 receptor site function was studied. The incubation of WI-38 fibroblasts with dexamethasone sodium sulfate produces the biphasic
mode of action, i.e., the growth-stimulating phase with low doses (90–230 μg/ml) and the growth-inhibiting phase with high
doses (450–900 μg/ml). The function of C3 receptor sites on WI-38 fibroblasts seems to be very stable and cannot be suppressed by the pretreatment of WI-38 fibroblasts
with dexamethasone in high concentrations, where the cell growth is inhibited. 相似文献
64.
SGS1 encodes a protein having DNA helicase activity, and a mutant allele of SGS1 was identified as a suppressor of the slow growth phenotype of top3 mutants. In this study, we examined whether Sgs1 prevents formation of DNA double strand breaks (DSBs) or is involved in DSB repair following exposure to methyl methanesulfonate (MMS). An analysis by pulsed-field gel electrophoresis and epistasis analyses indicated that Sgs1 is required for DSB repair that involves Rad52. In addition, analyses on the relationship between Sgs1 and proteins involved in DSB repair suggested that Sgs1 and Mre11 function via independent pathways both of which require Rad52. In sgs1 mutants, interchromosomal heteroallelic recombination and sister chromatid recombination (SCR) were not induced upon exposure to MMS, though both were induced in wild type cells, indicating the involvement of Sgs1 in heteroallelic recombination and SCR. Surprisingly, the ability of Sgs1 to bind to DNA topoisomerase III (Top3) was absolutely required for the induction of heteroallelic recombination and SCR and suppression of MMS sensitivity but its helicase activity was not, suggesting that Top3 plays a more important role in both recombinations than the DNA helicase activity of Sgs1. 相似文献
65.
Tajima K Han X Satoh Y Ishii A Araki Y Munekata M Taguchi S 《Applied microbiology and biotechnology》2012,94(2):365-376
Recently, we succeeded in isolating a thermotolerant bacterium, Pseudomonas sp. SG4502, which is capable of accumulating polyhydroxyalkanoate (PHA) even at 55 °C, as a source of thermostable enzymes.
In this study, we cloned a pha locus from the bacterium and identified two genes encoding PHA synthases (PhaC1SG and PhaC2SG). Two mutations, Ser324Thr and Gln480Lys, corresponding to those of a lactate (LA)-polymerizing enzyme (LPE) from mesophilic
Pseudomonas sp. 61-3 were introduced into PhaC1SG to evaluate the potential of the resulting protein as a “thermostable LPE”. The mutated PhaC1SG [PhaC1SG(STQK)] showed high thermal stability in synthesizing P(LA-co-3HB) in an in vitro reaction system under a range of high temperatures. Requirement of 3HBCoA as a priming unit for LA polymerization
by the LPE has been suggested in both of the in vitro and in vivo experiments. Based on the finding, the PhaC1SG(STQK)-mediated synthesis of a LA-based copolymer with a block sequence was achieved in the in vitro system by sequential
feeding of the corresponding two substrates. This in vitro reaction system using the thermostable LPE provides us with a versatile
way to synthesize the various types of LA-based copolymers with desired sequence patterns, random or block, depending on the
way of supplying hydroxyalkanoates (mixed or sequential feeding). 相似文献
66.
67.
Megumi Narukawa‐Nara Ayako Nakamura Ko Kikuzato Yusuke Kakei Akiko Sato Yuka Mitani Yumiko Yamasaki‐Kokudo Takahiro Ishii Ken‐ichiro Hayashi Tadao Asami Takehiko Ogura Shigeo Yoshida Shozo Fujioka Takashi Kamakura Tsutomu Kawatsu Masanori Tachikawa Kazuo Soeno Yukihisa Shimada 《The Plant journal : for cell and molecular biology》2016,87(3):245-257
We previously reported l ‐α‐aminooxy‐phenylpropionic acid (AOPP) to be an inhibitor of auxin biosynthesis, but its precise molecular target was not identified. In this study we found that AOPP targets TRYPTOPHAN AMINOTRANSFERASE of ARABIDOPSIS 1 (TAA1). We then synthesized 14 novel compounds derived from AOPP to study the structure–activity relationships of TAA1 inhibitors in vitro. The aminooxy and carboxy groups of the compounds were essential for inhibition of TAA1 in vitro. Docking simulation analysis revealed that the inhibitory activity of the compounds was correlated with their binding energy with TAA1. These active compounds reduced the endogenous indole‐3‐acetic acid (IAA) content upon application to Arabidopsis seedlings. Among the compounds, we selected 2‐(aminooxy)‐3‐(naphthalen‐2‐yl)propanoic acid (KOK1169/AONP) and analyzed its activities in vitro and in vivo. Arabidopsis seedlings treated with KOK1169 showed typical auxin‐deficient phenotypes, which were reversed by exogenous IAA. In vitro and in vivo experiments indicated that KOK1169 is more specific for TAA1 than other enzymes, such as phenylalanine ammonia‐lyase. We further tested 41 novel compounds with aminooxy and carboxy groups to which we added protection groups to increase their calculated hydrophobicity. Most of these compounds decreased the endogenous auxin level to a greater degree than the original compounds, and resulted in a maximum reduction of about 90% in the endogenous IAA level in Arabidopsis seedlings. We conclude that the newly developed compounds constitute a class of inhibitors of TAA1. We designated them ‘pyruvamine’. 相似文献
68.
Olivier Honnay Beatrijs Bossuyt Hans Jacquemyn Ayako Shimono Kentaro Uchiyama 《Oikos》2008,117(1):1-5
There are indications that a persistent seed bank can protect small and isolated plant populations from local extinction. Genetic mechanisms contributing to this phenomenon are the increase of local effective population size – and hence the decrease of genetic drift – through a reservoir of persistent seeds, and the accumulation of intergenerational genetic diversity in the seed bank. To find evidence for these mechanisms, we conducted two formal meta-analyses. First, we analyzed 42 published habitat fragmentation studies and investigated whether the degree of genetic differentiation between fragmented plant populations was mediated by seed longevity. Second, we reviewed 13 published studies reporting the genetic diversity of both the seed bank and the above ground plants, aiming at comparing genetic diversity contained in the seed bank with the above ground vegetation. We conclude that a persistent seed bank may indeed mitigate the consequences of habitat fragmentation and protect a species from genetic drift and population genetic differentiation. We found no evidence, however, of high levels of genetic diversity accumulating in the soil seed bank. If genetic differences are present between the standing crop and the seed bank, they are very likely the result of local selection acting either directly or indirectly as a filter on the alleles present in the seed bank. We finally suggest that 1) the role of the seed bank should not be neglected in habitat fragmentation studies and 2) it is not very fruitful to continue comparing seed bank genetic diversity with above ground plant genetic diversity, unless this is performed under different selection regimes. 相似文献
69.
Nobuyuki Sugioka Hikaru Odani Toshio Ohta Hideki Kishimoto Tadaki Yasumura Kanji Takada 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1994,654(2)
Mycophenolate mofetil, a new immunosuppressant, is a morpholinoethyl ester of mycophenolic acid. A new selective, sensitive and simple high-performance liquid chromatographic method was developed for the determination of mycophenolic acid and mycophenolate mofetil in biological samples. The preparation of samples was based on liquid—liquid extraction. The compounds were separated on a CN column using acetonitrile—0.01 M phosphate buffer (1:4, v/v) as the mobile phase. UV detection was used at wavelengths 215 and 304 nm. The detection limit was 5 ng per injection volume. This method enabled pharmacokinetic and pharmacodynamic studies in humans and rats. 相似文献
70.
Baker DL Fujiwara Y Pigg KR Tsukahara R Kobayashi S Murofushi H Uchiyama A Murakami-Murofushi K Koh E Bandle RW Byun HS Bittman R Fan D Murph M Mills GB Tigyi G 《The Journal of biological chemistry》2006,281(32):22786-22793
Autotaxin (ATX, nucleotide pyrophosphate/phosphodiesterase-2) is an autocrine motility factor initially characterized from A2058 melanoma cell-conditioned medium. ATX is known to contribute to cancer cell survival, growth, and invasion. Recently ATX was shown to be responsible for the lysophospholipase D activity that generates lysophosphatidic acid (LPA). Production of LPA is sufficient to explain the effects of ATX on tumor cells. Cyclic phosphatidic acid (cPA) is a naturally occurring analog of LPA in which the sn-2 hydroxy group forms a 5-membered ring with the sn-3 phosphate. Cellular responses to cPA generally oppose those of LPA despite activation of apparently overlapping receptor populations, suggesting that cPA also activates cellular targets distinct from LPA receptors. cPA has previously been shown to inhibit tumor cell invasion in vitro and cancer cell metastasis in vivo. However, the mechanism governing this effect remains unresolved. Here we show that 3-carba analogs of cPA lack significant agonist activity at LPA receptors yet are potent inhibitors of ATX activity, LPA production, and A2058 melanoma cell invasion in vitro and B16F10 melanoma cell metastasis in vivo. 相似文献