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41.
Kawachi A Ichihara K Hisanaga S Iida J Toyota H Hotani H Itoh TJ 《Biochemical and biophysical research communications》2003,305(1):72-78
To see a molecular basis of the difference in the microtubule binding between MAP2 and MAP4, we compared the binding of them onto microtubule and Zinc-sheet in the presence of various concentrations of NaCl. The Zinc-sheet is the lateral association of protofilaments arranged in an antiparallel fashion with alternatively exposed opposite surfaces, so that binding requiring adjacent protofilaments is restricted. While the salt-dependence of the MAP2 desorption was not altered between these tubulin polymers, MAP4 dissociated from Zinc-sheet at lower concentrations of NaCl than from microtubule. These results suggest that single protofilament is sufficient for microtubule binding of MAP2 as observed by Al-Bassam et al. [J. Cell Biol. 157 (2002) 1187], but MAP4 appeared to interact with adjacent protofilaments during microtubule-binding. Weakened binding on Zinc-sheets was also observed in the projection domain-deletion mutants of MAP4, so that the difference in the protofilament-dependence would lie in the relatively conserved microtubule-binding domain. 相似文献
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43.
Kenichiro Kinouchi Atsuhiro Ichihara Motoaki Sano Ge-Hong Sun-Wada Yoh Wada Hiroki Ochi Toru Fukuda Kanako Bokuda Hideaki Kurosawa Naohiro Yoshida Shu Takeda Keiichi Fukuda Hiroshi Itoh 《PloS one》2013,8(11)
The ATPase 6 accessory protein 2 (ATP6AP2)/(pro)renin receptor (PRR) is essential for the biogenesis of active vacuolar H+-ATPase (V-ATPase). Genetic deletion of ATP6AP2/PRR causes V-ATPase dysfunction and compromises vesicular acidification. Here, we characterized the domains of ATP6AP2/PRR involved in active V-ATPase biogenesis. Three forms of ATP6AP2/PRR were found intracellularly: full-length protein and the N- and C-terminal fragments of furin cleavage products, with the N-terminal fragment secreted extracellularly. Genetic deletion of ATP6AP2/PRR did not affect the protein stability of V-ATPase subunits. The extracellular domain (ECD) and transmembrane domain (TM) of ATP6AP2/PRR were indispensable for the biogenesis of active V-ATPase. A deletion mutant of ATP6AP2/PRR, which lacks exon 4-encoded amino acids inside the ECD (Δ4M) and causes X-linked mental retardation Hedera type (MRXSH) and X-linked parkinsonism with spasticity (XPDS) in humans, was defective as a V-ATPase-associated protein. Prorenin had no effect on the biogenesis of active V-ATPase. The cleavage of ATP6AP2/PRR by furin seemed also dispensable for the biogenesis of active V-ATPase. We conclude that the N-terminal ECD of ATP6AP2/PRR, which is also involved in binding to prorenin or renin, is required for the biogenesis of active V-ATPase. The V-ATPase assembly occurs prior to its delivery to the trans-Golgi network and hence shedding of ATP6AP2/PRR would not affect the biogenesis of active V-ATPase. 相似文献
44.
45.
Vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are homologous neuropeptides which share vasodilatory properties. This paper addresses the question of whether PHI exerts its vascular action via a receptor distinct from that for VIP. Radioligand binding experiments were done using [Tyr(125I)10]VIP, [Tyr(125I)22]porcine PHI, [Tyr(125I)10]rat PHI and arterial preparations from rat, bovine and porcine species. The radioiodination of rat PHI by the lactoperoxidase-glucose oxidase method and analysis of the structure of the major radiolabeled derivatives were described. All the receptor binding experiments identified a VIP-preferring receptor irrespective of which radioligand or arterial preparation was utilized. VIP and PHI peptides demonstrated cross-desensitization in studies of relaxation of porcine coronary arterial strips in vitro. The present results favor the conclusion that the vascular actions of the PHI peptides are best explained by binding to a VIP-preferring receptor. 相似文献
46.
Toshio Itoh T. Tanaka Ryozo Nagai Tetsuro Kamiya Toshitami Sawayama Toshio Nakayama Hitonobu Tomoike Harumizu Sakurada Yoshio Yazaki Yusuke Nakamura 《Human genetics》1998,102(4):435-439
Familial long QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent
syncopal attacks, and sudden death may occur as a result of ventricular tachyarrhythmias. Three genes responsible for this
syndrome (KVLQT1, HERG, and SCN5A) have been identified so far, and mutations have been reported on the basis of partially characterized genomic organization.
To optimize the search for HERG mutations, we have determined the genomic structure of HERG and investigated mutations in LQTS families. Human genomic clones containing the HERG gene were isolated from a human genomic library by using reverse-transcribed polymerase chain reaction (RT-PCR) products
from this gene as probes. We determined exon/intron boundaries and flanking intronic sequences by using primers synthesized
on the basis of the HERG cDNA sequence available in the DNA database. HERG was shown to consist of 15 exons spanning approximately 19 kb on chromosome 7q35. Subsequently, we synthesized oligonucleotide
primers to cover the entire coding region and searched for mutations in 36 Japanese LQTS families. When genomic DNA from each
proband was examined by the PCR/single-strand conformation polymorphism technique followed by direct DNA sequencing, five
novel mutations were detected. Each mutation was present in affected relatives of the respective proband. This work should
increase the efficiency of screening mutations associated with HERG.
Received: 4 November 1997 / Accepted: 5 January 1998 相似文献
47.
Simple determination of mycophenolic acid in human serum by column-switching high-performance liquid chromatography 总被引:4,自引:0,他引:4
Teshima D Kitagawa N Otsubo K Makino K Itoh Y Oishi R 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2002,780(1):21-26
A column-switching high-performance liquid chromatographic analysis was established to monitor the serum concentration of mycophenolic acid, the active metabolite from mycophenolate mofetil administered for the prophylaxis of acute organ rejection in renal transplantation. The system consisted of two pumps for solvent delivery, a column-switching valve, a precolumn, and a reversed-phase analytical column. The present method enabled us to determine MPA by injecting serum samples directly into HPLC without any pretreatment. The mobile phases with different amounts of organic solvent were delivered to the precolumn and analytical column by separate lines, and samples were applied to the precolumn. The column switching valves were switched automatically following the processes for the elimination of protein and the drug analysis. The peak heights of MPA were linearly related to the concentrations (r=0.999) in the range of 0.1-20 micro g/ml, and the limit of quantification was 0.1 micro g/ml (S/N ratio=3). This method was accurate and reproducible on the basis of the results of recovery (94.0-98.0%) and small coefficient of variations of intra and inter-assay (less than 8.3%). 相似文献
48.
Local and global cerebral blood flow and glucose utilization in the α-galactosidase A knockout mouse model of Fabry disease 总被引:2,自引:0,他引:2
Yoshiaki Itoh Takanori Esaki Michelle Cook Pankaj Qasba † Kazuaki Shimoji § Joseph Alroy ‡ Roscoe O. Brady † Louis Sokoloff David F. Moore† 《Journal of neurochemistry》2001,79(6):1217-1224
Fabry disease is an X-linked lysosomal disorder characterized by deficient alpha-galactosidase A activity and intracellular accumulations of glycosphingolipids, mainly globotriaosylceramide (Gb3). Clinically, patients occasionally present CNS dysfunction. To examine the pathophysiology underlying brain dysfunction, we examined glucose utilization (CMR(glc)) and cerebral blood flow (CBF) globally and locally in 18 brain structures in the alpha-galactosidase A gene knockout mouse. Global CMR(glc) was statistically significantly reduced by 22% in Fabry mice (p < 0.01). All 18 structures showed decreases in local CMR(glc) ranging from 14% to 33%. The decreases in all structures of the diencephalon, caudate-putamen, brain stem, and cerebellar cortex were statistically significant (p < 0.05). Global cerebral blood flow (CBF) and local CBF measured in the same 18 structures were lower in Fabry mice than in control mice, but none statistically significantly. Histological examination of brain revealed no cerebral infarcts but abundant Gb3 deposits in the walls of the cerebral vessels with neuronal deposits localized to the medulla oblongata. These results indicate an impairment in cerebral energy metabolism in the Fabry mice, but one not necessarily due to circulatory insufficiency. 相似文献
49.
Inage-Miyake Y Shimanuki S Itoh T Murakami Y Kimura M Suzuki H Miyake M Toki D Uenishi H Awata T Hamasima N 《Biochemical genetics》2005,43(1-2):79-85
We have obtained a partial cDNA and three BAC clones for the porcine insulin-like growth factor binding protein 1 gene (IGFBP-1). Results of fluorescence in situ and radiation hybrid (RH) mapping assigned this gene to porcine chromosome (SSC) 18q24-qter. We found two types of polymerase chain reaction–restriction-fragment-length polymorphisms (PCR–RFLP) in intron 2 by using FokI and AluI. 相似文献
50.
Kawano T Chen L Watanabe SY Yamauchi J Kaziro Y Nakajima Y Nakajima S Itoh H 《FEBS letters》1999,452(3):355-359
Arachidonic acid (AA) is generated via Rac-mediated phospholipase A2 (PLA2) activation in response to growth factors and cytokines and is implicated in cell growth and gene expression. In this study, we show that AA activates the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in a time- and dose-dependent manner. Indomethacin and nordihydroguaiaretic acid, potent inhibitors of cyclooxygenase and lipoxygenase, respectively, did not exert inhibitory effects on AA-induced SAPK/JNK activation, thereby indicating that AA itself could activate SAPK/JNK. As Rac mediates SAPK/JNK activation in response to a variety of stressful stimuli, we examined whether the activation of SAPK/JNK by AA is mediated by Rac1. We observed that AA-induced SAPK/JNK activation was significantly inhibited in Rat2-Rac1N17 dominant-negative mutant cells. Furthermore, treatment of AA induced membrane ruffling and production of hydrogen peroxide, which could be prevented by Rac1N17. These results suggest that AA acts as an upstream signal molecule of Rac, whose activation leads to SAPK/JNK activation, membrane ruffling and hydrogen peroxide production. 相似文献