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931.
Jun Yu Sui Zhang Eagle S.H. Chu Minnie Y.Y. Go Rebecca H.Y. Lau Junhong Zhao Chung-Wah Wu Lixin Tong Jingmin Zhao Terence C.W. Poon Joseph J.Y. Sung 《The international journal of biochemistry & cell biology》2010,42(6):948-957
Nonalcoholic steatohepatitis with fibrosis is a more severe form of nonalcoholic fatty liver disease, one of the most common liver diseases. We have previously shown that peroxisome proliferator-activated receptors gamma (PPARγ) ligand, rosiglitazone, prevented the development of the methionine choline deficient (MCD) diet-induced fibrosing steatohepatitis. We have now tested whether overexpression of PPARγ ameliorates established steatohepatitis and fibrosis. Male C57BL6 mice fed with MCD diet for 8 weeks developed hepatic fibrosis with increased hepatic expression of collagen1α(I), inhibitors of fibrosis reversal-1, regulator involved in matrix degradation-9 and connective tissue growth factor. After 2 weeks of transduction of PPARγ through an adenovirus-expressing PPARγ (Ad-PPARγ), expression of these genes was reduced in a manner that paralleled the reduction in activated hepatic stellate cells (HSCs) and resolution of liver fibrosis. On the in vitro study, PPARγ is expressed in primary quiescent HSC, but depleted in culture activated HSC. Conversely, ectopic expression of PPARγ in activated HSC achieved the phenotypic reversal to the quiescent cell. Such induction markedly suppressed cell viability and cell proliferation, downregulated proliferating cell nuclear antigen, and caused cell cycle arrest at G0/G1 phase. Further, introduction of PPARγ in HSC increased cell apoptosis, this was confirmed by enhanced expression of FasL, cleaved caspase-3, cleaved caspase-7 and poly ADP-ribose polymerase, indicating an extrinsic apoptosis pathway. In conclusion, the present study shows that MCD diet-induced fibrosing steatohepatitis can be reversed by overexpression of PPARγ. It is likely that PPARγ reverses fibrosis by reducing HSCs proliferation, inducing cell cycle arrest and apoptosis. 相似文献
932.
Background
Direct in vivo investigation of human metabolism is complicated by the distinct metabolic functions of various sub-cellular organelles. Diverse micro-environments in different organelles may lead to distinct functions of the same protein and the use of different enzymes for the same metabolic reaction. To better understand the complexity in the human metabolism, a compartmentalized human metabolic network with integrated sub-cellular location information is required. 相似文献933.
Yu W Dener JM Dickman DA Grothaus P Ling Y Liu L Havel C Malesky K Mahajan T O'Brian C Shelton EJ Sperandio D Tong Z Yee R Mordenti JJ 《Bioorganic & medicinal chemistry letters》2006,16(15):4053-4058
The metabolites of the tryptase inhibitor CRA-9249 were identified after exposure to liver microsomes. CRA-9249 was found to be degraded rapidly in liver microsomes from rabbit, dog, cynomolgus monkey, and human, and less rapidly in microsomes from rat. The key metabolites included cleavage of an aryl ether, in addition to an unexpected hydroxylation of the amide side chain adjacent to the amide nitrogen. The chemical structures of both metabolites were confirmed by synthesis and comparison to material isolated from the liver microsomes. Several suspected hydroxylated metabolites were also synthesized and analyzed as part of the structure identification process. 相似文献
934.
935.
上海市树附生苔藓植物生态位 总被引:8,自引:1,他引:7
生态位理论在植被生态研究中有着重要的应用价值,引入生态位理论对树附生苔藓植物进行了研究。在上海市市区和郊区主要公园、部分街道及校园,包括崇明岛等地区,共设立18个样点,调查发现43种树附生苔藓植物,其中藓类植物39种,苔类植物4种。根据盖度值计算了43种树附生苔藓植物的生态位宽度。结果表明,树附生苔藓植物种数(N)与生态位宽度(B)符合公式N=0.3423e-0.0369B,r=0.9347,大部分的树附生植物生态位宽度很窄,67.44%种类的生态位宽度小于0.1。本文计算了43种树附生苔藓植物的生态位重叠值,应用主分量分析法和最小生成树法对它们进行分类。将43种树附生苔藓植物分成3个生态类群,它们与生境关系显著。因此,在苔藓植物保护中应特别注意对树附生苔藓植物及其生境的保护。 相似文献
936.
Yeast has proven to be a powerful system for investigation of chromatin structure. However, the extent to which yeast chromatin can serve as a model for mammalian chromatin is limited by the significant number of differences that have been reported. To further investigate the structural relationship between the two chromatins, we have performed a DNA topological analysis of pRSSVO, a 5889 base-pair plasmid that can replicate in either yeast or mammalian cells. When grown in mammalian cells, pRSSVO contains an average of 33 negative supercoils, consistent with one nucleosome per 181 bp. This is close to the measured nucleosome repeat length of 190 bp. However, when grown in yeast cells, pRSSVO contains an average of only 23 negative supercoils, which is indicative of only one nucleosome per 256 bp. This is dramatically different from the measured nucleosome repeat length of 165 bp. To account for these observations, we suggest that yeast chromatin is composed of relatively short ordered arrays of nucleosomes with a repeat of 165 bp, separated by substantial gaps, possibly corresponding to regulatory regions. 相似文献
937.
The nucleus accumbens, situated at the junction between rostral pre-commissural caudate and putamen, is now considered to be critically involved in rewarding and motivational functions mediated by the neurotransmitter dopamine. However, in the human, the precise anatomical boundaries of this nucleus are still undetermined and controversy exists as to the extent to which nucleus accumbens activity is controlled by noradrenaline, a related neurotransmitter now much neglected (in favor of dopamine) by the scientific community. Here we resolve the question of noradrenaline in the human nucleus accumbens and identify, in autopsied brain of normal subjects, a small subdivision of the caudomedial portion of this nucleus that selectively contains strikingly high levels of noradrenaline and thus represents the only area in human brain having equally high levels of both noradrenaline and dopamine. The presence of very high, localized noradrenaline concentrations in the caudomedial nucleus accumbens implies a special biological role for this neurotransmitter in human brain motivational processes. 相似文献
938.
939.
O'Brien JE Peterson TJ Tong MH Lee EJ Pfaff LE Hewitt SC Korach KS Weiss J Jameson JL 《The Journal of biological chemistry》2006,281(36):26683-26692
940.
Gadd45a interacts with aurora-A and inhibits its kinase activity 总被引:4,自引:0,他引:4
Shao S Wang Y Jin S Song Y Wang X Fan W Zhao Z Fu M Tong T Dong L Fan F Xu N Zhan Q 《The Journal of biological chemistry》2006,281(39):28943-28950
Centrosome stability is required for successful mitosis in mammalian cells. Amplification of the centrosome leads to chromosomal missegregation and generation of aneuploidy, which are closely associated with cell transformation and tumorigenesis (Doxsey, S. J. (2001) Nat. Cell Biol. 3, E105-E108; Hinchcliffe, E. H., and Sluder, G. (2001) Genes Dev. 15, 1167-1181; Pihan, G. A., Purohit, A., Wallace, J., Malhotra, R., Liotta, L., and Doxsey, S. J. (2001) Cancer Res. 61, 2212-2219). However, there are currently limited insights into mechanism(s) for this critical biological event. Here we show that Gadd45a, a DNA damage-inducible protein that is regulated by tumor suppressors p53 and BRCA1, participates in the maintenance of centrosome stability. Mouse embryonic fibroblasts derived from gadd45a knock-out mice exhibit centrosome amplification (designated as increased centrosome numbers). Introduction of exogenous Gadd45a into mouse embryonic fibroblasts isolated from gadd45a-null mice substantially restored the normal centrosome profile. In contrast to p21(waf1/cip1), which ensures coordinated initiation of centrosome, Gadd45a had no significant effect on centrosome duplication in S phase. Interestingly Gadd45a was found to physically associate with Aurora-A protein kinase, whose deregulated expression results in centrosome abnormality. Furthermore Gadd45a was demonstrated to strongly inhibit Aurora-A kinase activity and to antagonize Aurora-A-induced centrosome amplification. These findings identify a novel mechanism for Gadd45a in the maintenance of centrosome stability and broaden understandings of p53- and BRCA1-regulated signaling pathways in maintaining genomic fidelity. 相似文献