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951.
Miura K Yang L van Rooijen N Ohnishi H Seki E 《American journal of physiology. Gastrointestinal and liver physiology》2012,302(11):G1310-G1321
Inflammatory cell infiltration in the liver is a hallmark of nonalcoholic steatohepatitis (NASH). The chemokine-chemokine receptor interaction induces inflammatory cell recruitment. CC-chemokine receptor (CCR)2 is expressed on hepatic macrophages and hepatic stellate cells. This study aims to investigate the therapeutic potential of CCR2 to NASH. Twenty-two weeks on a choline-deficient amino acid-defined (CDAA) diet induced steatosis, inflammatory cell infiltration, and liver fibrosis with increased CCR2 and monocyte chemoattractant protein (MCP)-1 expression in the wild-type livers. The infiltrated macrophages expressed CD68, CCR2, and a marker of bone marrow-derived monocytes, Ly6C. CCR2(-/-) mice had less steatosis, inflammatory cell infiltration, and fibrosis, and hepatic macrophages expressing CD68 and Ly6C were decreased. Toll-like receptor (TLR)4(-/-), TLR9(-/-), and MyD88(-/-) mice had reduced hepatic macrophage infiltration with decreased MCP-1 and CCR2 expression because TLR signaling is a potent inducer of MCP-1. To assess the role of Kupffer cells at the onset of NASH, Kupffer cells were depleted by liposomal clodronate. The Kupffer cell depletion ameliorated steatohepatitis with a decrease in the MCP-1 expression and recruitment of Ly6C-expressing macrophages at the onset of NASH. Finally, to test the therapeutic potential of targeting CCR2, a CCR2 inhibitor was administered to mice on a CDAA diet. The pharmaceutical inhibition of CCR2 prevented infiltration of the Ly6C-positive macrophages, resulting in an inhibition of liver inflammation and fibrosis. We concluded that CCR2 and Kupffer cells contribute to the progression of NASH by recruiting bone marrow-derived monocytes. 相似文献
952.
Ido Y Yamamoto T Yoshitomi T Yamamoto A Obana E Ohkura K Shinohara Y 《Mammalian genome》2012,23(3-4):286-293
BLAST analysis of the rat genome revealed the presence of 16 pseudogenes of isoform 1 of the mitochondrial voltage-dependent anion channel (VDAC1). Based on their structural characterization, it was concluded that these pseudogenes were formed by integration of VDAC1 cDNA into the genome, and subsequent rearrangements/mutations. By RT-PCR analysis using carefully designed primers that could not amplify the cDNA of genuine VDAC1, 8 of these 16 pseudogenes showed slight expression in certain tissues, but none of them seemed to encode a functional protein. 相似文献
953.
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955.
Tojo T Spears GW Tsuji K Nishimura H Ogino T Seki N Sugiyama A Matsuo M 《Bioorganic & medicinal chemistry letters》2002,12(17):2427-2430
A series of quinoline-3-carbothioamides and their analogues was prepared via four synthetic routes and evaluated for their antinephritic and immunomodulating activities. The optimal compound 9g strongly inhibited the T-cell independent antibody production in mice immunized with TNP-LPS and was highly effective in two nephritis models, namely chronic graft-versus-host disease and autoimmune MRL/l mice. 相似文献
956.
Irie T Seki T 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2002,131(2):209-219
Retinoids in the eggs of four teleosts, chum salmon (Oncorhynchus keta), black porgy (Acanthopagrus schlegeli), marbled flounder (Pleuronectes yokohamae), and stingfish (Inimicus japonicus), were analyzed by high performance liquid chromatography. Retinal (RAL1) or both RAL1 and 3,4-didehydroretinal (RAL2) were major or exclusive retinoids in the eggs of every species examined. In O. keta eggs, both RAL1 and RAL2 were present at the ratio of approximately 3:4, whereas RAL1 was the only retinal in the eggs of the other three marine species. RAL1 was the exclusive retinoid in the eggs of P. yokohamae and I. japonicus, whose eggs lack lipid bodies. In the eggs of O. keta and A. schlegeli, which have lipid bodies, retinylesters were also detected, and retinals composed 69% and 93%, respectively, of total retinoids. In O. keta eggs, retinals were present mostly in the aqueous part and were bound to a protein homologous to lipovitellin 1, an amphibian yolk protein, and retinylesters were located in lipids. These results indicate that retinals are the essential mode of retinoid storage in eggs of teleosts and they are the precursors of functional retinoids, such as retinoic acid and visual pigment chromophores. Retinylesters are additional retinoids that accompany lipid accumulation. 相似文献
957.
Mashino T Nishikawa D Takahashi K Usui N Yamori T Seki M Endo T Mochizuki M 《Bioorganic & medicinal chemistry letters》2003,13(24):4395-4397
We examined the antibacterial and antiproliferative activities of alkylated C60-bis(N,N-dimethylpyrrolidinium iodide) derivatives. The fullerene derivatives inhibited bacteria and cancer cell growth effectively. However, the fullerene derivatives with a long alkyl chain did not show antibacterial activity. 相似文献
958.
MMS4 of Saccharomyces cerevisiae was originally identified as the gene responsible for one of the collection of methyl methanesulfonate (MMS)-sensitive mutants, mms4. Recently it was identified as a synthetic lethal gene with an SGS1 mutation. Epistatic analyses revealed that MMS4 is involved in a pathway leading to homologous recombination requiring Rad52 or in the recombination itself, in which SGS1 is also involved. MMS sensitivity of mms4 but not sgs1, was suppressed by introducing a bacterial Holliday junction (HJ) resolvase, RusA. The frequencies of spontaneously occurring unequal sister chromatid recombination (SCR) and loss of marker in the rDNA in haploid mms4 cells and interchromosomal recombination between heteroalleles in diploid mms4 cells were essentially the same as those of wild-type cells. Although UV- and MMS-induced interchromosomal recombination was defective in sgs1 diploid cells, hyper-induction of interchromosomal recombination was observed in diploid mms4 cells, indicating that the function of Mms4 is dispensable for this type of recombination. 相似文献
959.
Yoshinori Utsumi Tetsuya Sakurai Yoshimi Umemura Sarah Ayling Manabu Ishitani Jarunya Narangajavana Punchapat Sojikul Kanokporn Triwitayakorn Minami Matsui Ri-ichiroh Manabe Kazuo Shinozaki Motoaki Seki 《Tropical plant biology》2012,5(1):110-116
Cassava (Manihot esculenta Crantz) is an important tropical root crop that provides food security and income generation for many farmers. Cassava ranks as the third most important source of calories in the tropics and provides sustenance to 800 million people worldwide. Cassava is also an efficient source of modified starch and bioethanol. In spite of the many advantages and high potential of cassava, the research community lacks functional genomic resources. Therefore, RIKEN has been working to establish a cassava functional genomics platform, which includes full-length cDNAs, DNA microarrays, transformation capabilities, and a searchable database in collaboration with the International Center for Tropical Agriculture (CIAT) of Colombia and Mahidol University of Thailand. In this review, we summarize the present status and future perspectives of our cassava functional genomic approaches. 相似文献
960.
Hirotaka Takahashi Akihiko Ozawa Keiichirou Nemoto Akira NozawaMotoaki Seki Kazuo ShinozakiHiroyuki Takeda Yaeta Endo Tatsuya Sawasaki 《FEBS letters》2012,586(19):3134-3141
Plant genome possesses over 100 protein phosphatase (PPase) genes that are key regulators of signal transduction via phosphorylation/dephosphorylation event. Here we report a comprehensive functional analysis of protein serine/threonine, dual-specificity and tyrosine phosphatases using recombinant PPases produced by wheat cell-free protein synthesis system. Eighty-two recombinant PPases were successfully produced using Arabidopsis full-length cDNA as templates. In vitro PPase assay was performed using phosphorylated myelin basic protein as substrate. Among the AtPPases examined, 26 serine/threonine, three dual-specificity and one tyrosine PPases exhibited catalytic activity, including 20 serine/threonine and one dual-specificity PPases that showed in vitro activities for the first time. Our study demonstrates genome-wide biochemical analysis of AtPPases using wheat cell-free system, and provides new information and insights on enzyme activities.