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51.
Miyazaki H Oyama F Wong HK Kaneko K Sakurai T Tamaoka A Nukina N 《Biochemical and biophysical research communications》2007,361(1):43-48
Processing of APP by BACE1 plays a crucial role in the pathogenesis of Alzheimer disease (AD). Recently, the voltage-gated sodium channel (Nav) β4 subunit (β4), an auxiliary subunit of Nav that is supposed to serve as a cell adhesion molecule, has been identified as a substrate for BACE1. However, the biological consequence of BACE1 processing of β4 remains illusive. Here, we report the biological effects of β4 processing by BACE1. Overexpression of β4 in Neuro2a cells promoted neurite extension and increased the number of F-actin rich filopodia-like protrusions. While coexpression of BACE1 together with β4 further accelerated neurite extension, the number of filopodia-like protrusions was reduced. Overexpression of C-terminal fragment of β4 that was generated by BACE1 (β4-CTF) partially recapitulated the results obtained with BACE1 overexpression. These results suggest that the processing of β4 by BACE1 regulates neurite length and filopodia-like protrusion density in neurons. 相似文献
52.
Iwanaga S Yamasaki N Kimura M Kouzuma Y 《Bioscience, biotechnology, and biochemistry》2005,69(1):220-223
Plant Kunitz-type protease inhibitors contain a conserved Asn residue in the N-terminal region. To investigate the role of Asn residue in protease inhibitory activities, Erythrina variegata trypsin inhibitor a (ETIa), E. variegata chymotrypsin inhibitor (ECI), and their mutants, ETIa-N12A and ECI-N13A, were used. Both mutants exhibit weaker inhibitory activities toward their cognate proteases than the wild-type proteins and were readily cleaved at reactive sites. Furthermore, kinetic analysis of the interactions of the mutated proteins with their cognate proteases by surface plasmon resonance (SPR) measurement indicated that replacements of the Asn residue mainly affected dissociation rate constants. The conserved Asn residues of Kunitz-type inhibitors play an important role in exhibiting effective inhibitory activity by stabilizing the structures of the primary binding loop and protease-inhibitor complex. 相似文献
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Maruf Mohammad Akbor Koji Tomobe Tomomi Yamada Juhyon Kim Hiroki Mano Nobuyuki Kurosawa Kazuo Sasaki Yasuyuki Nomura Masaharu Isobe 《Biochemical and biophysical research communications》2013
The senescence-accelerated mouse prone 8 (SAMP8) strain exhibits age-related learning and memory deficits (LMD) at 2 months of age. Combined linkage analysis of 264 F2 intercross SAMP8 × JF1 mice and RNA-seq analysis identified Hcn1 gene out of 29 genes in the LMD region on chromosome 13. Hcn1 in SAMP8 strain showed 15 times less polyglutamine repetition compared to Japanese fancy mouse 1 (JF1). Whole cell patch clamp analysis showed that Hcn1 ion conductivity was significantly lower in SAMP8 compared to that of JF1, which may be associated with learning and memory deficiency. 相似文献
56.
Activation of peroxisome proliferator-activated receptor-alpha stimulates both differentiation and fatty acid oxidation in adipocytes 总被引:1,自引:0,他引:1
Goto T Lee JY Teraminami A Kim YI Hirai S Uemura T Inoue H Takahashi N Kawada T 《Journal of lipid research》2011,52(5):873-884
Peroxisome proliferator-activated receptor-α (PPARα) is a dietary lipid sensor, whose activation results in hypolipidemic effects. In this study, we investigated whether PPARα activation affects energy metabolism in white adipose tissue (WAT). Activation of PPARα by its agonist (bezafibrate) markedly reduced adiposity in KK mice fed a high-fat diet. In 3T3-L1 adipocytes, addition of GW7647, a highly specific PPARα agonist, during adipocyte differentiation enhanced glycerol-3-phosphate dehydrogenase activity, insulin-stimulated glucose uptake, and adipogenic gene expression. However, triglyceride accumulation was not increased by PPARα activation. PPARα activation induced expression of target genes involved in FA oxidation and stimulated FA oxidation. In WAT of KK mice treated with bezafibrate, both adipogenic and FA oxidation-related genes were significantly upregulated. These changes in mRNA expression were not observed in PPARα-deficient mice. Bezafibrate treatment enhanced FA oxidation in isolated adipocytes, suppressing adipocyte hypertrophy. Chromatin immunoprecipitation (ChIP) assay revealed that PPARα was recruited to promoter regions of both adipogenic and FA oxidation-related genes in the presence of GW7647 in 3T3-L1 adipocytes. These findings indicate that the activation of PPARα affects energy metabolism in adipocytes, and PPARα activation in WAT may contribute to the clinical effects of fibrate drugs. 相似文献
57.
Oarada M Tsuduki T Suzuki T Miyazawa T Nikawa T Hong-quan G Kurita N 《Biochimica et biophysica acta》2003,1622(3):151-160
The effect of dietary docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on host resistance to Paracoccidioides brasiliensis infection was investigated. Mice fed palm oil supplemented with DHA showed reduced antifungal activity in the spleen and liver, as compared with mice fed palm oil or soybean oil without supplementation with DHA. Mice fed DHA-supplemented soybean oil also showed reduced antifungal activity in the liver, but the extent of reduction was less profound. This reduction in antifungal activity was not observed with EPA-supplemented palm or EPA-supplemented soybean oil. These results suggest that two factors, DHA and palm oil in combination, are involved in reducing the host resistance. DHA-enriched palm oil was also responsible for an increase in DHA concentration and a marked decrease in arachidonic acid content in the spleen and liver. However, this group did not show elevated spleen and liver phospholipid hydroperoxide levels compared with the other groups, excluding the possibility that the reduction in antifungal activity observed with DHA-enriched palm oil is due to acceleration of in vivo lipid peroxidation. Greater infection-induced increases in spleen and serum interferon-gamma concentrations were observed in mice fed DHA-enriched palm oil compared with the other groups. 相似文献
58.
Tohru Kobayashi Yasushi Kageyama Nobuyuki Sumitomo Katsuhisa Saeki Tsuyoshi Shirai Susumu Ito 《World journal of microbiology & biotechnology》2005,21(6-7):961-967
Summary Crystallographic analysis of the highly alkaline M-protease from an alkaliphilic Bacillus strain shows the occurrence of a unique salt bridge triad Arg19–Glu271–Arg275 (in subtilisin BPN′ numbering), which is not
found in less alkaline true subtilisins BPN′ and Carlsberg from Bacillus amyloliquefaciens and Bacillus licheniformis, respectively. Because the corresponding residues are all Gln residue in the subtilisin BPN′, Gln residue was engineered
into the position(s) 19, 271 and/or 275 in M-protease by site-directed mutagenesis. Disruptions of the salt bridge caused
the reduction of the thermostability of the mutant proteins at alkaline pH with the following decreasing order of thermal
inactivation rate; the wild-type > Arg275 → Gln > Glu271 → Gln > Arg19 → Gln/Glu271 → Gln/Arg275 → Gln > Arg19 → Gln. This
result provides the evidence that the salt bridge triad contributes to the thermostability and structural rigidity of the
highly alkaline M-protease. 相似文献
59.
不同育苗方式对移栽后侧柏和白榆幼苗根系生长的影响 总被引:1,自引:0,他引:1
不同类型苗木,具有不同的根系结构特征,其根系结构也将影响林木的生长和恢复生态系统的稳定性。以侧柏和白榆为研究对象,对移栽18个月后的种基盘苗与营养钵苗根系的生长进行了调查。结果表明:侧柏种基盘苗的总根长和平均直径比营养钵苗分别增加了316.20 cm和0.05mm,白榆苗则分别增加了651.54 cm和0.88mm。侧柏和白榆种基盘苗的根系表面积比营养钵苗分别增加了40.05%和73.04%。侧柏种基盘苗的根系总体积与营养钵苗的差异不显著,而白榆种基盘苗的根系总体积则比营养钵苗增加了54.70%。侧柏和白榆营养钵苗的一级侧根数量大于种基盘苗,增幅分别为42.31%和30.65%。对于侧柏来说,营养钵苗的根尖总数比种基盘苗的增加324个,但白榆苗差异不显著。各种处理的幼苗总根长与根系表面积都有显著相关性,但与根体积不具有显著相关性。营养钵苗的根系平均直径和根尖数量具有相对独立性,而种基盘的根系平均直径与总根长以及根体积均表现为显著相关。种基盘苗能提高侧柏、白榆幼苗的根冠比,促进幼苗株高、地径和主根的生长。采用种基盘苗进行植被恢复,由于其具有较大的根表面积和根长度,林木便具有了较大的吸收水分和营养的能力,以及较高的固结表层土壤能力。 相似文献
60.