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51.
Gu J Zhao Y Isaji T Shibukawa Y Ihara H Takahashi M Ikeda Y Miyoshi E Honke K Taniguchi N 《Glycobiology》2004,14(2):177-186
A rat pheochromocytoma cell line (PC12), when transfected with beta1,4-N-acetylglucosaminyltransferase III (GnT-III), which catalyzes the formation of a bisecting GlcNAc structure in N-glycans, resulted in the suppression of neurite outgrowth induced by costimulation of epidermal growth factor (EGF) and integrins. The neurite outgrowth was restored by the overexpression of a constitutively activated mitogen- or extracellular signal-regulated kinase kinase-1 (MEK-1). Consistent with this, the EGF receptor (EGFR)-mediated ERK activation was blocked in GnT-III transfectants. Conversely, the overexpression of dominant negative MEK-1 or treatment with PD98059, a specific inhibitor of MEK-1, inhibited neurite outgrowth in controls transfected with mock. Furthermore GnT-III activity is required for these inhibitions, because the overexpression of a dominant negative GnT-III mutant (D321A) failed to reduce neurite outgrowth and EGFR-mediated ERK activation. Lectin blot analysis confirmed that EGFR from wild-type GnT-III transfectants had been modified by bisecting GlcNAc in its N-glycan structures. This modification led to a significant decrease in EGF binding and EGFR autophosphorylation. Collectively, the results constitute a comprehensive body of evidence to show clearly that the overexpression of GnT-III prevents neurite outgrowth induced by costimulation of EGF and integrins through the Ras/MAPK activation pathway and indicates that GnT-III may be an important regulator for cell differentiation in neural tissues. 相似文献
52.
Abe M Kenmochi A Ichimaru N Hamada T Nishioka T Miyoshi H 《Bioorganic & medicinal chemistry letters》2004,14(3):779-782
The presence of two hydroxy groups adjacent to the THF ring(s) is a common structural feature of natural acetogenins. To elucidate the role of each hydroxy group in the inhibitory action of acetogenins, we synthesized three acetogenin analogues which lack either or both of the hydroxy groups, and investigated their inhibitory activities with bovine heart mitochondrial complex I. Our results indicate that the presence of either of the two hydroxy groups sufficiently sustains a potent inhibitory effect. 相似文献
53.
Konno H Hiura N Makabe H Abe M Miyoshi H 《Bioorganic & medicinal chemistry letters》2004,14(3):629-632
To elucidate the inhibitory action of acetogenins, we synthesized an acetogenin derivative which possesses tetraol in place of the tetrahydrofuran ring and examined its inhibitory activity against bovine heart mitochondrial complex I. Our results indicate that these hydroxy groups are an essential structural factor though it is not effective as bis-THF hydroxy groups combination. 相似文献
54.
Recent progress in complex I research suggests that a wide variety of complex I inhibitors share a common large binding domain with partially overlapping sites. To verify this concept, we carried out real-time displacement tests of a fluorescent ligand with various competitors using a novel quinazoline-type inhibitor (aminoquinazoline, AQ). In the presence of an excess amount of the competitors, the binding of AQ to the enzyme was completely suppressed, being in line with the concept mentioned above. However, AQ bound to the enzyme was not displaced by subsequent addition of an increasing amount of competitors in the concentration range expected from the relative magnitude of the K(d) values of AQ and competitors, rather, much higher concentrations of the competitors were needed to displace bound AQ. These results cannot be explained merely by the premise of a common or partially overlapping binding site(s) between AQ and competitors. On the other hand, double-inhibitor titration of steady state complex I activity suggested that additivity of inhibition is not necessarily observed for all pairs of complex I inhibitors. Our results are discussed in light of the cooperativity of the inhibitor binding sites. 相似文献
55.
Preferential paternal origin of microdeletions caused by prezygotic chromosome or chromatid rearrangements in Sotos syndrome 总被引:3,自引:0,他引:3
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Miyake N Kurotaki N Sugawara H Shimokawa O Harada N Kondoh T Tsukahara M Ishikiriyama S Sonoda T Miyoshi Y Sakazume S Fukushima Y Ohashi H Nagai T Kawame H Kurosawa K Touyama M Shiihara T Okamoto N Nishimoto J Yoshiura K Ohta T Kishino T Niikawa N Matsumoto N 《American journal of human genetics》2003,72(5):1331-1337
Sotos syndrome (SoS) is characterized by pre- and postnatal overgrowth with advanced bone age; a dysmorphic face with macrocephaly and pointed chin; large hands and feet; mental retardation; and possible susceptibility to tumors. It has been shown that the major cause of SoS is haploinsufficiency of the NSD1 gene at 5q35, because the majority of patients had either a common microdeletion including NSD1 or a truncated type of point mutation in NSD1. In the present study, we traced the parental origin of the microdeletions in 26 patients with SoS by the use of 16 microsatellite markers at or flanking the commonly deleted region. Deletions in 18 of the 20 informative cases occurred in the paternally derived chromosome 5, whereas those in the maternally derived chromosome were found in only two cases. Haplotyping analysis of the marker loci revealed that the paternal deletion in five of seven informative cases and the maternal deletion in one case arose through an intrachromosomal rearrangement, and two other cases of the paternal deletion involved an interchromosomal event, suggesting that the common microdeletion observed in SoS did not occur through a uniform mechanism but preferentially arose prezygotically. 相似文献
56.
Adachi A Shinjyo N Fujita D Miyoshi H Amino H Watanabe Yi Kita K 《FEBS letters》2003,543(1-3):174-178
Caenorhabditis elegans CLK-1 was identified from long-lived mutant worms, and is believed to be involved in ubiquinone biosynthesis. The protein belongs to the eukaryotic CLK-1/Coq7p family, which is also similar to the bacterial Coq7 family, that hydroxylates demethoxyubiquinone, resulting in the formation of hydroxyubiquinone, a precursor of ubiquinone. In Escherichia coli, the corresponding reaction is catalyzed by UbiF, a member of a distinct class of hydroxylase. Although previous studies suggested that the eukaryotic CLK-1/Coq7 family is a hydroxylase of demethoxyubiquinone, there was no direct evidence to show the enzymatic activity of the eukaryotic CLK-1/Coq7 family. Here we show that the plasmid encoding C. elegans CLK-1 supported aerobic respiration on a non-fermentable carbon source of E. coli ubiF mutant strain and rescued the ability to synthesize ubiquinone, suggesting that the eukaryotic CLK-1/Coq7p family could function as bacterial UbiF. 相似文献
57.
58.
Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction 总被引:2,自引:0,他引:2
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Tanaka M Miyoshi J Ishizaki H Togawa A Ohnishi K Endo K Matsubara K Mizoguchi A Nagano T Sato M Sasaki T Takai Y 《Molecular biology of the cell》2001,12(5):1421-1430
The Rab3 small G protein family consists of four members, Rab3A, -3B, -3C, and -3D. Of these members, Rab3A regulates Ca(2+)-dependent neurotransmitter release. These small G proteins are activated by Rab3 GDP/GTP exchange protein (Rab3 GEP). To determine the function of Rab3 GEP during neurotransmitter release, we have knocked out Rab3 GEP in mice. Rab3 GEP-/- mice developed normally but died immediately after birth. Embryos at E18.5 showed no evoked action potentials of the diaphragm and gastrocnemius muscles in response to electrical stimulation of the phrenic and sciatic nerves, respectively. In contrast, axonal conduction of the spinal cord and the phrenic nerve was not impaired. Total numbers of synaptic vesicles, especially those docked at the presynaptic plasma membrane, were reduced at the neuromuscular junction approximately 10-fold compared with controls, whereas postsynaptic structures and functions appeared normal. Thus, Rab3 GEP is essential for neurotransmitter release and probably for formation and trafficking of the synaptic vesicles. 相似文献
59.
Ahn O Miyoshi K Itoh JI Nagato Y Kurata N 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2002,105(5):654-659
The rice heterochronic gene plastochron1, pla1, shows shorter plastochron and ectopic expression of the vegetative program during the rice reproductive phase resulting in aberrant panicle formation. A genetic and physical map was constructed to isolate the causal gene for the pla1 syndrome. Small-scale mapping was carried out to determine the approximate map position of the pla1 locus, and then a high-resolution genetic map was made for pla1-1, one of the pla1 alleles, using an F2 population comprising 578 pla1-1 homozygous plants. In a high-resolution genetic map, the pla1-1 locus was found to map between RFLP markers C961 and R1738A on chromosome 10, within a 3.6-cM genetic distance. A physical map encompassing the pla1-1 locus was constructed by overlapping Bacterial Artificial Chromosome (BAC) clones through chromosome walking. PCR-based RFLP markers from BAC-end clones were developed and mapped relative to the pla1 locus. Physical map construction using BAC clones indicated that a BAC clone, B44A10 (167-kb), contained the pla1 locus within 74-kb corresponding to a 0.52-cM genetic distance. Gene prediction of 74-kb region carrying the pla1 locus suggested several candidate genes for the pla1 gene. Identification of a candidate gene for pla1 will be made by sequence analysis of allele variation and cDNA screening. 相似文献
60.