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991.
Takehashi M Tada M Kanatsu-Shinohara M Morimoto H Kazuki Y Oshimura M Tada T Shinohara T 《Biology of reproduction》2012,86(6):178
Somatic cell hybridization is widely used to study the control of gene regulation and the stability of differentiated states. In contrast, the application of this method to germ cells has been limited in part because of an inability to culture germ cells. In this study, we produced germ cell hybrids using germ-line stem (GS) cells and multipotent germ-line stem (mGS) cells. While GS cells are enriched for spermatogonial stem cell (SSC) activity, mGS cells are similar to embryonic stem (ES) cells and originally derived from GS cells. Hybrids were successfully obtained between GS cells and ES cells, between GS cells and mGS cells, and between mGS cells and thymocytes. All exhibited ES cell markers and a behavior similar to ES cells, formed teratomas, and differentiated into somatic cell tissues. However, none of the hybrid cells were able to reconstitute spermatogenesis after microinjection into seminiferous tubules. Analyses of the DNA methylation patterns of imprinted genes also showed that mGS cells do not possess a DNA demethylation ability, which was found in embryonic germ cells derived from primordial germ cells. However, mGS cells reactivated the X chromosome and induced Pou5f1 expression in female thymocytes in a manner similar to ES cells. These data show that mGS cells possess ES-like reprogramming potential, which predominates over-SSC activity. 相似文献
992.
993.
Yoshinaga Y Mochizuki K Goda T 《Biochemical and biophysical research communications》2012,419(4):605-611
We previously reported that fructose force-feeding rapidly induces jejunal Slc2a5 gene expression in rats. In this study, we conducted microarray analyses using total RNA to identify genes upregulated in rat jejunum by fructose force-feeding. Rats were force-fed fructose, glucose or distilled water for 6h. Genes such as Slc2a5, Cdkn1c, Cabp2, Ranbp3, Vwce and Gcgr were induced by force-feeding with fructose compared with glucose or distilled water. Chromatin immunoprecipitation assays revealed that trimethylation of histone H3K4, and acetylation of histones H3 and H4, on the transcribed region of these fructose-inducible genes were enhanced by force-feeding of fructose, but not glucose or distilled water. These results suggest that the induction of genes in the rat jejunum by fructose force-feeding is coordinately regulated by histone modifications, particularly trimethylation of histone H3K4. 相似文献
994.
995.
Kyoko Nakamura Toshiaki Kogame Hiroyuki Oshiumi Akira Shinohara Yoshiki Sumitomo Keli Agama Yves Pommier Kimiko M. Tsutsui Ken Tsutsui Edgar Hartsuiker Tomoo Ogi Shunichi Takeda Yoshihito Taniguchi 《PLoS genetics》2010,6(1)
Topoisomerase inhibitors such as camptothecin and etoposide are used as anti-cancer drugs and induce double-strand breaks (DSBs) in genomic DNA in cycling cells. These DSBs are often covalently bound with polypeptides at the 3′ and 5′ ends. Such modifications must be eliminated before DSB repair can take place, but it remains elusive which nucleases are involved in this process. Previous studies show that CtIP plays a critical role in the generation of 3′ single-strand overhang at “clean” DSBs, thus initiating homologous recombination (HR)–dependent DSB repair. To analyze the function of CtIP in detail, we conditionally disrupted the CtIP gene in the chicken DT40 cell line. We found that CtIP is essential for cellular proliferation as well as for the formation of 3′ single-strand overhang, similar to what is observed in DT40 cells deficient in the Mre11/Rad50/Nbs1 complex. We also generated DT40 cell line harboring CtIP with an alanine substitution at residue Ser332, which is required for interaction with BRCA1. Although the resulting CtIPS332A/−/− cells exhibited accumulation of RPA and Rad51 upon DNA damage, and were proficient in HR, they showed a marked hypersensitivity to camptothecin and etoposide in comparison with CtIP+/−/− cells. Finally, CtIPS332A/−/−BRCA1−/− and CtIP+/−/−BRCA1−/− showed similar sensitivities to these reagents. Taken together, our data indicate that, in addition to its function in HR, CtIP plays a role in cellular tolerance to topoisomerase inhibitors. We propose that the BRCA1-CtIP complex plays a role in the nuclease-mediated elimination of oligonucleotides covalently bound to polypeptides from DSBs, thereby facilitating subsequent DSB repair. 相似文献
996.
997.
Miyaji K Nagao K Bannai M Asakawa H Kohyama K Ohtsu D Terasawa F Ito S Iwao H Ohtani N Ohta M 《PloS one》2010,5(11):e13808
From an evolutionary perspective, the ancestors of cetaceans first lived in terrestrial environments prior to adapting to aquatic environments. Whereas anatomical and morphological adaptations to aquatic environments have been well studied, few studies have focused on physiological changes. We focused on plasma amino acid concentrations (aminograms) since they show distinct patterns under various physiological conditions. Plasma and urine aminograms were obtained from bottlenose dolphins, pacific white-sided dolphins, Risso's dolphins, false-killer whales and C57BL/6J and ICR mice. Hierarchical cluster analyses were employed to uncover a multitude of amino acid relationships among different species, which can help us understand the complex interrelations comprising metabolic adaptations. The cetacean aminograms formed a cluster that was markedly distinguishable from the mouse cluster, indicating that cetaceans and terrestrial mammals have quite different metabolic machinery for amino acids. Levels of carnosine and 3-methylhistidine, both of which are antioxidants, were substantially higher in cetaceans. Urea was markedly elevated in cetaceans, whereas the level of urea cycle-related amino acids was lower. Because diving mammals must cope with high rates of reactive oxygen species generation due to alterations in apnea/reoxygenation and ischemia-reperfusion processes, high concentrations of antioxidative amino acids are advantageous. Moreover, shifting the set point of urea cycle may be an adaptation used for body water conservation in the hyperosmotic sea water environment, because urea functions as a major blood osmolyte. Furthermore, since dolphins are kept in many aquariums for observation, the evaluation of these aminograms may provide useful diagnostic indices for the assessment of cetacean health in artificial environments in the future. 相似文献
998.
Mie Shinohara Maria D. Ybanez Sanda Win Tin Aung Than Shilpa Jain William A. Gaarde Derick Han Neil Kaplowitz 《The Journal of biological chemistry》2010,285(11):8244-8255
Previously we demonstrated that c-Jun N-terminal kinase (JNK) plays a central role in acetaminophen (APAP)-induced liver injury. In the current work, we examined other possible signaling pathways that may also contribute to APAP hepatotoxicity. APAP treatment to mice caused glycogen synthase kinase-3β (GSK-3β) activation and translocation to mitochondria during the initial phase of APAP-induced liver injury (∼1 h). The silencing of GSK-3β, but not Akt-2 (protein kinase B) or glycogen synthase kinase-3α (GSK-3α), using antisense significantly protected mice from APAP-induced liver injury. The silencing of GSK-3β affected several key pathways important in conferring protection against APAP-induced liver injury. APAP treatment was observed to promote the loss of glutamate cysteine ligase (GCL, rate-limiting enzyme in GSH synthesis) in liver. The silencing of GSK-3β decreased the loss of hepatic GCL, and promoted greater GSH recovery in liver following APAP treatment. Silencing JNK1 and -2 also prevented the loss of GCL. APAP treatment also resulted in GSK-3β translocation to mitochondria and the degradation of myeloid cell leukemia sequence 1 (Mcl-1) in mitochondrial membranes in liver. The silencing of GSK-3β reduced Mcl-1 degradation caused by APAP treatment. The silencing of GSK-3β also resulted in an inhibition of the early phase (0–2 h), and blunted the late phase (after 4 h) of JNK activation and translocation to mitochondria in liver following APAP treatment. Taken together our results suggest that activation of GSK-3β is a key mediator of the initial phase of APAP-induced liver injury through modulating GCL and Mcl-1 degradation, as well as JNK activation in liver. 相似文献
999.
Expression of bacterial tyrosine ammonia-lyase creates a novel p-coumaric acid pathway in the biosynthesis of phenylpropanoids in Arabidopsis 总被引:2,自引:0,他引:2
Yasutaka Nishiyama Choong-Soo Yun Fumio Matsuda Tadamasa Sasaki Kazuki Saito Yuzuru Tozawa 《Planta》2010,232(1):209-218
Some flavonoids are considered as beneficial compounds because they exhibit anticancer or antioxidant activity. In higher
plants, flavonoids are secondary metabolites that are derived from phenylpropanoid biosynthetic pathway. A large number of
phenylpropanoids are generated from p-coumaric acid, which is a derivative of the primary metabolite, phenylalanine. The first two steps in the phenylpropanoid
biosynthetic pathway are catalyzed by phenylalanine ammonia-lyase and cinnamate 4-hydroxylase, and the coupling of these two
enzymes forms a rate-limiting step in the pathway. For the generation of p-coumaric acid, the conversion from phenylalanine to p-coumaric acid that is catalyzed by two enzymes can be theoretically performed by a single enzyme, tyrosine ammonia-lyase
(TAL) that catalyzes the conversion of tyrosine to p-coumaric acid in certain bacteria. To modify the p-coumaric acid pathway in plants, we isolated a gene encoding TAL from a photosynthetic bacterium, Rhodobacter sphaeroides, and introduced the gene (RsTAL) in Arabidopsis thaliana. Analysis of metabolites revealed that the ectopic over-expression of RsTAL leads to higher accumulation of anthocyanins in transgenic 5-day-old seedlings. On the other hand, 21-day-old seedlings of
plants expressing RsTAL showed accumulation of higher amount of quercetin glycosides, sinapoyl and p-coumaroyl derivatives than control. These results indicate that ectopic expression of the RsTAL gene in Arabidopsis enhanced the metabolic flux into the phenylpropanoid pathway and resulted in increased accumulation of flavonoids and phenylpropanoids. 相似文献
1000.
Mochizuki K Shimada M Tanaka Y Fukaya N Goda T 《Bioscience, biotechnology, and biochemistry》2010,74(12):2470-2474
β(2) integrins (CD11s/CD18) promote the attachment of leukocytes to vascular endothelial cells. We performed in this study sucrose loading to rats with moderate postprandial hyperglycemia with/without once-daily dosing of the α-glucosidase inhibitor, miglitol, for 4 days under 4-h fasting conditions. The streptozotocin (STZ)-treated rats showed moderate postprandial hyperglycemia on days 1 and 4. The gene expression was higher for CD11a with fasting and 3-h postprandial on day 1, and with fasting on day 4, for CD11b with fasting on day 1 and 3-h postprandial on day 4, and for CD18 with fasting on days 1 and 4 in peripheral leukocytes from the STZ-treated rats than in peripheral leukocytes from the saline-treated rats. Miglitol reduced postprandial hyperglycemia and the gene expression of CD11a with fasting and of CD11b 3-h postprandial on day 4. These results indicate that inhibiting postprandial hyperglycemia reduced the mRNA expression of β(2) integrins in peripheral leukocytes of moderately postprandial hyperglycemic rats. 相似文献