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排序方式: 共有251条查询结果,搜索用时 406 毫秒
71.
Naotaka Izuo Nobuhiro Watanabe Yoshihiro Noda Takashi Saito Takaomi C. Saido Koutaro Yokote Harumi Hotta Takahiko Shimizu 《Aging cell》2023,22(11):e13994
Although insulin resistance increases the risk of Alzheimer's disease (AD), the mechanisms remain unclear, partly because no animal model exhibits the insulin-resistant phenotype without persistent hyperglycemia. Here we established an AD model with whole-body insulin resistance without persistent hyperglycemia (APP/IR-dKI mice) by crossbreeding constitutive knock-in mice with P1195L-mutated insulin receptor (IR-KI mice) and those with mutated amyloid precursor protein (AppNL-G-F mice: APP-KI mice). APP/IR-dKI mice exhibited cognitive impairment at an earlier age than APP-KI mice. Since cholinergic dysfunction is a major characteristic of AD, pharmacological interventions on the cholinergic system were performed to investigate the mechanism. Antagonism to a nicotinic acetylcholine receptor α7 (nAChRα7) suppressed cognitive function and cortical blood flow (CBF) response to cholinergic-regulated peripheral stimulation in APP-KI mice but not APP/IR-dKI mice. Cortical expression of Chrna7, encoding nAChRα7, was downregulated in APP/IR-dKI mice compared with APP-KI. Amyloid β burden did not differ between APP-KI and APP/IR-dKI mice. Therefore, insulin resistance, not persistent hyperglycemia, induces the earlier onset of cognitive dysfunction and CBF deregulation mediated by nAChRα7 downregulation. Our mouse model will help clarify the association between type 2 diabetes mellitus and AD. 相似文献
72.
Satoshi Toyoshima Takaomi Saido Fusao Makishima Toshiaki Osawa 《Biochemical and biophysical research communications》1983,114(3):1126-1131
Liposomes having membrane proteins of chicken erythrocytes were prepared and the effect of S-adenosylmethionine on 45Ca2+ uptake into the liposomes was investigated. S-Adenosylmethionine, a donor of methyl groups in enzymatic methylation, induced an increase of 45Ca2+ uptake into the proteoliposomes with membrane proteins but not into the liposomes without membrane proteins. Increased release of 45Ca2+ from the inside of the proteoliposomes was also induced by S-adenosylmethionine. These increases of uptake and release of 45Ca2+ were inhibited by S-adenosylhomocystein, an inhibitor of enzymatic methylation. Furthermore, membrane proteins from chicken erythrocytes showed protein and phospholipid methyltransferase activities. The uptake of other materials, 3-0-[methyl-3H]glucose, α-[1-14C]aminoisobutyric acid, 42K+ and 54Mn2+, into the proteoliposomes was not increased by S-adenosylmethionine. These results suggest that enzymatic methylation of membrane components may have an important role in the regulation of calcium transport in the chicken erythrocyte membrane and this regulation is rather specific for calcium. 相似文献
73.
74.
Dual Roles of Proteasome in the Metabolism of Presenilin 1 总被引:1,自引:0,他引:1
Toshiyuki Honda† Kaori Yasutake‡ Naomi Nihonmatsu Mark Mercken‡ Hiroshi Takahashi Ohoshi Murayama Miyuki Murayama Kazuki Sato‡ Akira Omori‡ Satoshi Tsubuki§ Takaomi C. Saido§ & Akihiko Takashima 《Journal of neurochemistry》1999,72(1):255-261
Abstract : Presenilin 1 (PS1) has been identified as a causative gene for most early-onset familial Alzheimer's disease. Biochemical studies revealed that PS1 exists predominantly as two processed fragments in cells and brain tissues. We prepared stably transfected cells expressing the wild-type and familial Alzheimer's disease-associated mutants of PS1 and investigated the enzyme that participates in the metabolism of PS1. After treatment of the cells with proteasome inhibitors, the full-length PS1 was significantly accumulated. The levels of N- and C-terminal fragments were also increased. The accumulation of PS1 with a deletion of exon 10, which is unable to be processed, on treatment of the transfected cells with lactacystin indicated that proteasome can degrade full-length PS1. A synthetic peptide that includes the processing region of PS1 was cleaved by 20S proteasome at the putative processing sites after Met288 and Glu299 . Metabolic labeling experiments showed that the appearance of the N-terminal fragment was attenuated by the inhibitor. Finally, 28-kDa N- and 20-kDa C-terminal fragments were generated by purified PS1 in vitro. These data indicated that the proteasome pathway is involved in PS1 processing. These results demonstrate that the proteasome pathway plays dual roles in processing and degradation of PS1. 相似文献
75.
76.
The migratory history of Sakhalin taimen, Hucho perryi, was examined in terms of strontium (Sr) and calcium (Ca) uptake in the otolith by using wavelength dispersive X-ray spectrometry on an electron microprobe. Otolioth Sr:Ca ratios of freshwater-reared samples remained consistently at low levels throughout the otolith. The Sr:Ca ratios of samples from Lake Aynskoye of Sakhalin Island showed a low value from the core up to a point of 700–2140µm. Thereafter, the ratios increased sharply and remained at higher levels up to the outermost regions. The difference in Sr:Ca ratio might be the result of the presence of individuals that underwent seawater and freshwater life history phases, probably reflecting the ambient salinity or the seawater–freshwater gradient in Sr concentration. Otolith Sr:Ca ratio analysis revealed downstream migration history in H. perryi. 相似文献
77.
Molecularly imprinted copolymer membranes functionalized by phase inversion imprinting for uracil recognition and permselective binding 总被引:1,自引:0,他引:1
Wang HY Xia SL Sun H Liu YK Cao SK Kobayashi T 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,804(1):127-134
Uracil (URA) was selected as a template for preparing molecularly imprinted membranes of poly(acrylonitrile-co-methylacrylic acid) [P(AN-co-MAA)] using the phase inversion technique. This study used Fourier transform infra-red (FT-IR) and (1)H nuclear magnetic resonance (NMR) spectroscopic studies to characterize the polymer-template interaction and scanning electron microscopy (SEM) and atomic force microscopy (AFM) for morphology of the URA imprinted membrane. Resultant membranes had typical ultrafiltration structure with porous morphology and showed a permeation flux of 3.5 x 10 9-5)m(3)/(m(2)s) for 32 microM URA aqueous solution. Permselective binding to the target molecule was observed in permeation experiments with 7.9 micromol/g binding capacity of URA. Binding selectivity was discussed for URA and its analogs, dimethyluracil (DMURA) and caffeine (CAF), with 0.6 and 0.8 micromol/g binding capacity, respectively. 相似文献
78.
Yohko U. Katagiri Kazuhiro Ohmi Chihiro Katagiri Takaomi Sekino Hideki Nakajima Tomohiko Ebata Nobutaka Kiyokawa Junichiro Fujimoto 《Glycoconjugate journal》2001,18(4):347-353
The binding of Shiga toxin (Stx) to Gb3Cer in detergent-insoluble microdomains (DIM)/raft of the ACHN human renal tubular cell line causes the temporal activation of the Src-family kinase Yes [1]. As a strategy for examining signaling mechanisms in DIM/raft, monoclonal antibodies (MAbs) are reliable tools for characterizing the constituent molecules in these microdomains. Thus, we employed DIM/raft suspensions of ACHN cells as an immunogen to develop MAbs. Simply subcutaneous injections of ACHN DIM/raft could elevate the serum titer after several boosts. The first screening was performed using dot-blot immunostaining with culture supernatants on a polyvinylidene difluoride (PVDF) membrane, on which DIM/raft or their chloroform/methanol (C/M) (2:1, v/v) extracts were dot-blotted. The next screening was performed by flowcytometric analysis of ACHN cells treated with or without a permeabilizing reagent. Many of the clones (21/31 clones=68%) thus obtained were also found to recognize to lipid fractions of the DIM/raft. Strikingly, all of the 21 clones that reacted to the lipid fraction were found to recognize monosialosyl galactosylgloboside (MSGG) or GL7, which carries the SSEA-4 epitope. Using DIM/raft as immunogens may enable us to easily obtain MAbs for glycolipids. 相似文献
79.
Inheritance Characteristics of Microsatellite DNA Loci in Experimental Families of Japanese Flounder Paralichthys olivaceus 总被引:3,自引:0,他引:3
Allele segregating patterns of microsatellite DNA loci in 5 experimental families of Japanese flounder Paralichthys olivaceus and genotype frequencies for deviation from Hardy-Weinberg expectations (HWE) in natural P. olivaceus populations were studied to assess inheritability. Of the 12 microsatellite loci examined, 1 locus had a possibility of scoring
errors of heterozygous individuals caused by unreproducible polymerase chain reaction amplifications of a particular allele.
At the remaining 11 loci, almost all of alleles were segregated according to Mendelian transmission, and observed genotype
frequencies in natural populations were consistent with HWE. The results demonstrated here would provide useful information
supporting the suitability of these microsatellite loci as inheritable P. olivaceus genetic markers.
Received September 25, 2000; accepted March 1, 2001 相似文献
80.
Analysis of Microsatellite DNA Polymorphisms in Rockfish Sebastes thompsoni and Application to Population Genetics Studies 总被引:1,自引:0,他引:1
Population differentiation and relationships among 6 natural rockfish populations collected from northern coastal seas around
Japan were assayed using microsatellite DNA loci. Seven loci examined were polymorphic in all populations. The number of alleles
per locus ranged from 6.7 to 9.3, and the average of observed and expected heterozygosity ranged from 0.63 to 0.68, and from
0.66 to 0.69, respectively. The observed genotype frequencies at each locus were almost in agreement with Hardy-Weinberg expectations
with two exceptions (P < .05). The allele frequencies of 16 population pairs were significantly different (P < .05). Genetic distance (D
A
) between 6 populations ranged from 0.03 to 0.08. According to a neighbor-joining tree generated from the D
A
values, the 6 populations fell into 3 clusters. These clusters were correlated with the geographical positions of each population;
larval dispersions due to water current were also found to have an effect on these results.
Received May 2, 2000; accepted July 17, 2000. 相似文献