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排序方式: 共有911条查询结果,搜索用时 343 毫秒
71.
Murata Y Tsuruzoe K Kawashima J Furukawa N Kondo T Motoshima H Igata M Taketa K Sasaki K Kishikawa H Kahn CR Toyonaga T Araki E 《Biochemical and biophysical research communications》2007,364(2):301-307
Insulin receptor substrate-1 (IRS-1) is the major substrate of both the insulin receptor and the IGF-1 receptor. In this study, we created IRS-1 transgenic (IRS-1-Tg) mice which express human IRS-1 cDNA under control of the mouse IRS-1 gene promoter. In the IRS-1-Tg mice, IRS-1 mRNA expression was significantly increased in almost all tissues, but its protein expression was increased in very limited tissues (epididymal fat and skeletal muscle). IRS-1-Tg mice showed glucose intolerance and significantly enlarged epididymal fat mass, as well as elevated serum TNF-α concentrations. Importantly insulin signaling was significantly attenuated in the liver of IRS-1-Tg mice, which may contribute to the glucose intolerance. Our results suggest that excess IRS-1 expression may not provide a beneficial impact on glucose homeostasis in vivo. 相似文献
72.
Terada Y Inoshita S Kuwana H Kobayashi T Okado T Ichijo H Sasaki S 《Biochemical and biophysical research communications》2007,364(4):1043-1049
We investigated the role of apoptosis signal-regulating kinase 1 (ASK1) in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Blood urea nitrogen (BUN) and serum creatinine were significantly higher in ASK1+/+ mice than in ASK1−/− mice after I/R injury. Renal histology of ASK1+/+ mice showed significantly greater tubular necrosis and degradation. In ASK1−/− mice, phosphorylation of ASK1, JNK, and p38K, and the number of TUNEL-positive cells and infiltrated leukocytes decreased after I/R injury. Apoptotic changes were significantly decreased in cultured renal tubular epithelial cells (TECs) from ASK1−/− mice under hypoxic condition. Transfection with dominant-active ASK1 induced apoptosis in TECs. Protein expression of monocyte chemoattractant protein-1 (MCP-1) was significantly weaker in ASK1−/− mice after I/R injury. Transfection with dominant negative-ASK1 significantly decreased MCP-1 production in TECs. These results demonstrated that ASK1 is activated in I/R-induced AKI, and blockage of ASK1 attenuates renal tubular apoptosis, MCP-1 expression, and renal function. 相似文献
73.
Kawai M Ando K Matsumoto Y Sakurada I Hirota M Nakamura H Ohta A Sudo M Hattori K Takashima T Hizue M Watanabe S Fujita I Mizutani M Kawamura M 《Bioorganic & medicinal chemistry letters》2007,17(20):5558-5562
(-)-6-[2-[4-(3-Fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone was identified as an orally active NR2B-subunit selective N-methyl-d-aspartate (NMDA) receptor antagonist. It has very high selectivity for NR2B subunits containing NMDA receptors versus the HERG-channel inhibition (therapeutic index=4200 vs NR2B binding IC(50)). This compound has improved pharmacokinetic properties compared to the prototype CP-101,606. 相似文献
74.
75.
Effects of dietary soybean peptides on hepatic production of ketone bodies and secretion of triglyceride by perfused rat liver 总被引:2,自引:0,他引:2
Tamaru S Kurayama T Sakono M Fukuda N Nakamori T Furuta H Tanaka K Sugano M 《Bioscience, biotechnology, and biochemistry》2007,71(10):2451-2457
Soybean protein isolate (SPI) was digested with protease to produce a peptides containing the low-molecular fraction (LD3) or a mixture of high- and low-molecular fractions (HD1). Rats were fed a diets containing SPI, LD3, or HD1 at a protein level equivalent to the 20% casein diet for 4 weeks. The serum triglyceride concentration was lower in rats fed SPI, LD3, and HD1 diets than in rats fed the casein diet, and the differences were significant for the cholesterol-enriched diet. The value for the LD3 group was the lowest among all groups for both the cholesterol-free and -enriched diets. The level of triglyceride in the post-perfused liver was significantly lower in the LD3 and HD1 groups and the SPI group than in the casein group irrespective of the presence of cholesterol in the diet. In the cholesterol-free diet, LD3 feeding as compared to casein feeding caused a reduction in triglyceride secretion from the liver to perfusate and an increment of hepatic ketone body production. The addition of cholesterol to the diets somewhat attenuated these effects of LD3. These results suggest that the low-molecular fraction in soybean peptides causes triglyceride-lowering activity through a reduction in triglyceride secretion from the liver to the blood circulation and the stimulation of fatty acid oxidation in the liver. There is a possibility that soybean peptides modulate triglyceride metabolism by changes in the hepatic contribution. 相似文献
76.
Immunohistochemical detection of hypoxia in mouse liver tissues treated with pimonidazole using “in vivo cryotechnique” 总被引:2,自引:2,他引:0
Wang J Olin M Rozell B Björkhem I Einarsson C Eggertsen G Gåfvels M 《Histochemistry and cell biology》2007,127(3):253-261
To evaluate hypoxic cells in live mouse liver tissues, immunohistochemistry for protein adducts of reductively activated pimonidazole
(PARaPi) was performed using the “in vivo cryotechnique (IVCT)” followed by freeze-substitution fixation. This method was
used because cryotechniques have some merits for examining biological events in living animal organs with improved time-resolution
compared to conventional perfusion and/or immersion chemical fixation. Pimonidazole was intraperitoneally injected into living
mice, and then after various times of hypoxia, their livers were quickly frozen by IVCT. The frozen liver tissues were freeze-substituted
in acetone containing 2% paraformaldehyde, and routinely embedded in paraffin wax. De-paraffinized sections were immunostained
for PARaPi. In liver tissues of mice without hypoxia, almost no immunostained cells were detected. However, in liver tissues
with 30 s of hypoxia, some hepatocytes in the pericentral zones were strongly immunostained. After 60 s of hypoxia, many hepatocytes
were immunostained with various degrees of staining intensity in all lobular zones, indicating different reactivities of pimonidazole
in the hepatocytes to hypoxia. At this time, the general immunoreactivity also appeared to be stronger around the central
veins than other portal areas. Although many hepatocytes were immunostained for PARaPi in the liver tissues with perfusion
fixation via heart, those with perfusion via portal vein were not immunostained. Thus, IVCT is useful to detect time-dependent
hypoxic states with pimonidazole treatment in living animal organs. 相似文献
77.
Yongxiang Zheng Fei Yu Yiming Wu Longlong Si Huan Xu Chuanling Zhang Qing Xia Sulong Xiao Qi Wang Qiuchen He Peng Chen Jiangyun Wang Kazunari Taira Lihe Zhang Demin Zhou 《Nucleic acids research》2015,43(11):e73
With the aim of broadening the versatility of lentiviral vectors as a tool in nucleic acid research, we expanded the genetic code in the propagation of lentiviral vectors for site-specific incorporation of chemical moieties with unique properties. Through systematic exploration of the structure–function relationship of lentiviral VSVg envelope by site-specific mutagenesis and incorporation of residues displaying azide- and diazirine-moieties, the modifiable sites on the vector surface were identified, with most at the PH domain that neither affects the expression of envelope protein nor propagation or infectivity of the progeny virus. Furthermore, via the incorporation of such chemical moieties, a variety of fluorescence probes, ligands, PEG and other functional molecules are conjugated, orthogonally and stoichiometrically, to the lentiviral vector. Using this methodology, a facile platform is established that is useful for tracking virus movement, targeting gene delivery and detecting virus–host interactions. This study may provide a new direction for rational design of lentiviral vectors, with significant impact on both basic research and therapeutic applications. 相似文献
78.
79.
In experiment 1 of this study, the interleukin-12 (IL-12)-inducing ability of six Enterococcus strains was evaluated in comparison with that of five Lactobacillus strains using murine splenocytes. At the same time, the involvement of Toll-like receptor (TLR) ligands in IL-12-inducing ability was assessed using splenocytes from TLR2-, TLR4- and MyD88-deficient mice. Most Enterococcus strains, especially Enterococcus faecalis strain EC-12, exerted higher IL-12-inducing ability compared with the Lactobacillus strains evaluated. Almost the same amount of IL-12 protein was produced by all lactic acid bacteria strains in splenocytes from TLR2- and TLR4-deficient mice, whereas splenocytes from MyD88-deficient mice showed no IL-12 production against all bacteria evaluated. In experiment 2, the role of TLR7, 8 and 9 ligands of E. faecalis strain EC-12 in the induction of IL-12 production was evaluated using murine macrophage cell line J774.1. A drastic decrease in IL-12-inducing ability was observed when heat-killed E. faecalis strain EC-12 was treated with nuclease, particularly RNase. In addition, less than one-tenth of IL-12 was produced by heat-killed E. faecalis strain EC-12 when both TLR7 and 9 were antagonized. These facts indicate that the nucleic acids of E. faecalis strain EC-12, particularly its RNA, are the potent TLR7 and 9 ligands that induce IL-12 production from antigen-presenting cells. 相似文献
80.
Ando T Semba K Suda H Sei A Mizuta H Araki M Abe K Imai K Nakagata N Araki K Yamamura K 《Mechanisms of development》2011,128(1-2):129-140
Danforth'sshort-tail (Sd) mouse is a semi-dominant mutation affecting the development of the vertebral column. Although the notochord degenerates completely by embryonic day 9.5, the vertebral column exists up to the lumber region, suggesting that the floor plate can substitute for notochord function. We previously established the mutant mouse line, Skt(Gt), through gene trap mutagenesis and identified the novel gene, Skt, which was mapped 0.95cM distal to the Sd locus. Taking advantage of the fact that monitoring notochordal development and genotyping of the Sd locus can be performed using the Skt(Gt) allele, we assessed the development of the vertebra, notochord, somite, floor plate and sclerotome in +-+/+-Skt(Gt), Sd-+/+-+, Sd-Skt(Gt)/+-+, Sd-Skt(Gt)/+-Skt(Gt), Sd-+/Sd-+ and Sd-Skt(Gt)/Sd-Skt(Gt) embryos. In Sd homozygous mutants with a C57BL/6 genetic background, the vertebral column was truncated in the 6th thoracic vertebra, which was more severe than previously reported. The floor plate and sclerotome developed to the level of somite before notochord degeneration and the number of remaining vertebrae corresponded well with the level of development of the floor plate and sclerotome. Defects to the sclerotome and subsequent vertebral development were not due to failure of somitogenesis. Taken together, these results suggest that the notochord induced floor plate development before degeneration, and that the remaining floor plate is sufficient for maintenance of differentiation of the somite into the sclerotome and vertebra in the absence of the notochord. 相似文献