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991.
Design and synthesis of 2,6-diprenyl-4-iodophenol TX-1952 with a novel and potent anti-peroxidative activity 总被引:1,自引:0,他引:1
Uto Y Hirata A Ishibashi M Nagasawa H Hori H 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2002,132(1):41-45
The structure-based elucidation of 2,4,6-tri-substituted phenols for their antioxidative and anti-peroxidative effects has been investigated using TX-1952 (2,6-diprenyl-4-iodophenol), TX-1961, TX-1980, BTBP and BHT. In the inhibition of mitochondrial lipid peroxidation, the inhibitory activity of 2,6-di-tert-butyl-4-bromophenol (BTBP) (IC(50)=0.17 microM) was twice as high as that of 2,6-di-tert-butyl-4-methylphenol (BHT) (IC(50)=0.31 microM). This result shows that the 4-halogen group increases inhibitory activity for mitochondrial lipid peroxidation. Besides, TX-1952 (IC(50)=0.60 microM) was the highest inhibitor among 2,6-diprenyl-4-halophenols, followed by TX-1961 (IC(50)=0.93 microM) and TX-1980 (IC(50)=1.2 microM). In 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging experiments, the activity of TX-1952 (IC(0.200)=53.1 microM) was lower than that of BHT (IC(0.200)=33.7 microM) and BTBP (IC(0.200)=16.0 microM), but TX-1952 and BHT showed the same HOMO energy (-8.991 eV). These results suggest that the two prenyl groups at ortho position hinder the phenolic hydrogen abstraction by DPPH radical. These findings demonstrated that TX-1952 was a novel and potent inhibitor for lipid peroxidation. 相似文献
992.
Nagasawa H Yamashita M Mikamo N Shimamura M Oka S Uto Y Hori H 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2002,132(1):33-40
For cancer therapy, hypoxia represents an important tumor specific target. Therefore we designed and synthesized antiangiogenic hypoxic cytotoxins as 'hypoxia modifiers'. They can be activated bioreductively in hypoxic cells to kill the oxygen-deficient tumor cells selectively and prevent their re-growth. The aromatic heterocycle di-N-oxides, tirapazamine (TPZ), TX-1102, and TX-402 inhibited growth of EMT6/KU cells, SAS/neo cells, and SAS/Trp248 cells (mutant p53 gene transformant) under hypoxic condition. They also induced apoptosis selectively at a dose of 10 microM each under hypoxic condition for 5 h. Their hypoxic cytotoxicities and apoptosis inducing activities were p53-independent because the activities in SAS/neo cells were almost similar to that in SAS/Trp248 cells. In angiogenesis inhibition assay using chick embryo chorioallantoic membrane (CAM), TPZ, TX-1102, TX-402 and TX-1033 showed 40, 25, 60 and 60% inhibition of angiogenesis each at a dose of 10 microg/CAM. On the other hand, the nitrosopyrimidine, TX-1041 had neither antiangiogenic activity nor cytotoxicity. Therefore the di-N-oxide group is thought to be required for the biological activities. TX-1102 was a potent antiangiogenic hypoxic cytotoxin inducing apoptosis p53-independently. 相似文献
993.
Cloning and characterization of the ferulic acid catabolic genes of Sphingomonas paucimobilis SYK-6 总被引:1,自引:0,他引:1
Masai E Harada K Peng X Kitayama H Katayama Y Fukuda M 《Applied and environmental microbiology》2002,68(9):4416-4424
Sphingomonas paucimobilis SYK-6 degrades ferulic acid to vanillin, and it is further metabolized through the protocatechuate 4,5-cleavage pathway. We obtained a Tn5 mutant of SYK-6, FA2, which was able to grow on vanillic acid but not on ferulic acid. A cosmid which complemented the growth deficiency of FA2 on ferulic acid was isolated. The 5.2-kb BamHI-EcoRI fragment in this cosmid conferred the transformation activity of ferulic acid to vanillin on Escherichia coli host cells. A sequencing analysis revealed the genes ferB and ferA in this fragment; these genes consist of 852- and 2,127-bp open reading frames, respectively. The deduced amino acid sequence of ferB showed 40 to 48% identity with that of the feruloyl-coenzyme A (CoA) hydratase/lyase genes of Pseudomonas and Amycolatopsis ferulic acid degraders. On the other hand, the deduced amino acid sequence of ferA showed no significant similarity to the feruloyl-CoA synthetase genes of other ferulic acid degraders. However, the deduced amino acid sequence of ferA did show 31% identity with pimeloyl-CoA synthetase of Pseudomonas mendocina 35, which has been classified as a new superfamily of acyl-CoA synthetase (ADP forming) with succinyl-CoA synthetase (L. B. Sánchez, M. Y. Galperin, and M. Müller, J. Biol. Chem. 275:5794-5803, 2000). On the basis of the enzyme activity of E. coli carrying each of these genes, ferA and ferB were shown to encode a feruloyl-CoA synthetase and feruloyl-CoA hydratase/lyase, respectively. p-coumaric acid, caffeic acid, and sinapinic acid were converted to their corresponding benzaldehyde derivatives by the cell extract containing FerA and FerB, thereby indicating their broad substrate specificities. We found a ferB homolog, ferB2, upstream of a 5-carboxyvanillic acid decarboxylase gene (ligW) involved in the degradation of 5,5'-dehydrodivanillic acid. The deduced amino acid sequence of ferB2 showed 49% identity with ferB, and its gene product showed feruloyl-CoA hydratase/lyase activity with a substrate specificity similar to that of FerB. Insertional inactivation of each fer gene in S. paucimobilis SYK-6 suggested that the ferA gene is essential and that ferB and ferB2 genes are involved in ferulic acid degradation. 相似文献
994.
Two-dimensional simulation of trabecular surface remodeling was conducted for a human proximal femur to investigate the structural change of cancellous bone toward a uniform stress state. Considering that a local mechanical stimulus plays an important role in cellular activities in bone remodeling, local stress nonuniformity was assumed to drive trabecular structural change to seek a uniform stress state. A large-scale pixel-based finite element model was used to simulate structural changes of individual trabeculae over the entire bone. As a result, the initial structure of trabeculae changed from isotropic to anisotropic due to trabecular microstructural changes caused by surface remodeling according to the mechanical environment in the proximal femur. Under a single-loading condition, it was shown that the apparent structural property evaluated by fabric ellipses corresponded to the apparent stress state in cancellous bone. As is observed in the actual bone, a distributed trabecular structure was obtained under a multiple-loading condition. Through these studies, it was concluded that trabecular surface remodeling toward a local uniform stress state at the trabecular level could naturally bring about functional adaptation phenomenon at the apparent tissue level. The proposed simulation model would be capable of providing insight into the hierarchical mechanism of trabecular surface remodeling at the microstructural level up to the apparent tissue level. 相似文献
995.
Matsumoto Y Tanaka K Hirata G Hanada M Matsuda S Shuto T Iwamoto Y 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(11):5824-5831
Vascular endothelial growth factor (VEGF) plays a crucial role in the pathogenesis of inflammatory joint disease, including angiogenesis and synovitis. Rheumatoid arthritis is a chronic inflammatory disease characterized by progressive synovitis and subsequent bone destruction mediated by osteoclasts (OCs). In this study, we investigate the effects of VEGF on OC precursor cells (pOCs) using Raw cells and adjuvant-induced arthritis in rats. OCs and pOCs in the arthritic joints express VEGF and VEGF receptor type I (Flt-1). Raw cells also express Flt-1, and VEGF treatment stimulated chemotaxis, cell proliferation, the association of Flt-1 with focal adhesion kinase (FAK), and the tyrosine phosphorylation of FAK in Raw cells. The tyrosine phosphorylation of FAK was also observed in pOCs in the arthritic joints of adjuvant-induced arthritis. Adenovirus-mediated expression of FAK-related nonkinase in Raw cells inhibited the effects of VEGF in a dominant negative manner. Furthermore, intra-articular injection of the FAK-related nonkinase virus suppressed the recruitment of pOCs and bone destruction. Our results suggest the possible involvement of the VEGF-Flt-1-FAK pathway in inflammatory disease-induced joint destruction. 相似文献
996.
The common myelolymphoid progenitor: a key intermediate stage in hemopoiesis generating T and B cells 总被引:3,自引:0,他引:3
Lu M Kawamoto H Katsube Y Ikawa T Katsura Y 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(7):3519-3525
We have previously shown that the common progenitors for myeloid, T, and B cell lineages are enriched in the earliest population of murine fetal liver. However, it remained unclear whether such multipotent progenitors represent the pluripotent progenitors capable of generating all hemopoietic cells or they also comprise progenitors restricted to myeloid, T, and B cell lineages. To address this issue, we have developed a new clonal assay covering myeloid, erythroid, T, and B cell lineages, and using this assay the developmental potential of individual cells in subpopulations of lineage marker-negative (Lin(-)) c-kit(+) murine fetal liver cells was investigated. We identified the progenitor generating myeloid, T, and B cells, but not erythroid cells in the Sca-1(high) subpopulation of Lin(-)c-kit(+) cells that can thus be designated as the common myelolymphoid progenitor (CMLP). Common myeloerythroid progenitors were also detected. These findings strongly suggest that the first branching point in fetal hemopoiesis is between the CMLP and common myeloerythroid progenitors. T and B cell progenitors may be derived from the CMLP through the previously identified myeloid/T and myeloid/B bipotent stages, respectively. 相似文献
997.
Kabututu Z Martin SK Nozaki T Kawazu S Okada T Munday CJ Duszenko M Lazarus M Thuita LW Urade Y Kubata BK 《International journal for parasitology》2002,32(14):66-1700
Lysates of Leishmania promastigotes can metabolise arachidonic acid to prostaglandins. Prostaglandin production was heat sensitive and not inhibited by aspirin or indomethacin. We cloned and sequenced the cDNA of Leishmania major, Leishmania donovani, and Leishmania tropica prostaglandin F(2alpha) synthase, and overexpressed their respective 34-kDa recombinant proteins that catalyse the reduction of 9,11-endoperoxide PGH(2) to PGF(2alpha). Database search and sequence alignment alignment showed that L. major prostaglandin F(2alpha) synthase exhibits 61, 99.3, and 99.3% identity with Trypanosoma brucei, L. donovani, and L. tropica prostaglandin F(2alpha) synthase, respectively. Using polymerase chain reaction amplification, Western blotting, and immunofluorescence, we have demonstrated that prostaglandin F(2alpha) synthase protein and gene are present in Old World and absent in New World Leishmania, and that this protein is localised to the promastigote cytosol. 相似文献
998.
Okano Y Inoue T Kubata BK Kabututu Z Urade Y Matsumura H Kai Y 《Journal of biochemistry》2002,132(6):859-861
Prostaglandin F(2 alpha) is a potent mediator of various physiological and pathological processes. Trypanosoma brucei prostaglandin F(2 alpha) synthase (TbPGFS) catalyzes the NADPH-dependent reduction of 9,11-endoperoxide PGH(2) to PGF(2 alpha), and could thus be involved in the elevation of the PGF(2 alpha) concentration during African trypanosomiasis. In the present report, the purification and crystallization of recombinant TbPGFS are described. The active recombinant enzyme was crystallized by the hanging-drop vapor-diffusion meth-od using ammonium sulfate as a precipitant. The crystal belonged to a tetragonal space group, P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters of a = b = 112.3 A, and c = 140.0 A. Native data up to 2.6 A resolution were collected from the crystal using our home facility. 相似文献
999.
Lee JR Takenaka H Takahashi N Makise M Yamaguchi Y Tsuchiya T Mizushima T 《Journal of biochemistry》2002,131(4):541-546
Origin Recognition Complex (ORC) is a candidate initiator of chromosomal DNA replication in eukaryotes. We recently reported that cardiolipin inhibits the interaction of Origin Recognition Complex ORC with origin DNA, as is the case of DnaA, the initiator of chromosomal DNA replication in prokaryotes. We report here that another acidic phospholipid, phosphatidylglycerol (PG), also inhibits the interaction. Synthetic PG with only unsaturated fatty acids inhibits ORC-binding to origin DNA more strongly than PG with only saturated fatty acids. On the other hand, phosphatidylcholine (neutral phospholipid) does not affect the ORC-origin interaction, regardless of the presence of saturated or unsaturated fatty acids. These results suggest that an acidic moiety and unsaturated fatty acids are important factors for the inhibitory effect of phospholipids on ORC binding to origin DNA, as is the case for DnaA. The inhibitory effect of cardiolipin on ORC binding to origin DNA was more apparent at 30 degrees C than at 4 degrees C. Furthermore, chlorpromazine restored the ORC-origin interaction in the presence of cardiolipin. Since the presence of unsaturated fatty acids, low incubation temperatures, and the addition of chlorpromazine all decrease membrane fluidity, these results suggest that membrane fluidity is important for the inhibitory effect of acidic phospholipids on ORC-binding to origin DNA, as is the case for DnaA. 相似文献
1000.
The function of SmpB protein in the trans-translation system was evaluated using the well-defined cell-free translation system consisting of purified ribosome, alanyl-tRNA synthetase and elongation factors. The analysis showed that SmpB protein enhances alanine-accepting activity of tmRNA and that SmpB protein and tmRNA are sufficient to complete the trans-translation process in the presence of translational components. Moreover, SmpB is indispensable in the addition of tag-peptide onto ribosomes by tmRNA. In particular, the A-site binding of tmRNA is inhibited in the absence of SmpB. 相似文献