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41.
Fujihara J Ueki M Yasuda T Iida R Soejima M Koda Y Kimura-Kataoka K Kato H Panduro A Tongu M Takeshita H 《DNA and cell biology》2011,30(4):205-217
The single-nucleotide polymorphisms (SNPs) in the human DNase I gene (DNASE1) might be involved in susceptibility to some common diseases; however, only limited population data are available. Further, the effects of these SNPs on in vivo DNase I activity remain unknown. The genotype and haplotype of all the SNPs in DNASE1 were determined in 3 ethnic groups including 14 populations using newly developed methods. Together with our previous data on the nonsynonymous SNPs, two major haplotypes based on the five exonic SNPs were identified; genetic diversity in the Asian population was low. Among 10 SNPs, other than exonic SNPs in the gene, only 3 were polymorphic among all the populations. Haplotype distribution, based on all the polymorphic SNPs, was clarified to be generally varied in an ethnic-dependent manner. Thus, the genetic aspects of DNASE1 with regard to all the SNPs in wide-ranging ethnic groups could be first demonstrated. Further, there was no correlation of all the polymorphic SNPs other than nonsynonymous ones with serum DNase I activity levels. Polymorphic SNPs other than the exonic SNPs might not be directly related to common diseases through alterations in in vivo levels of the activity. 相似文献
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Crystal structural characterization reveals novel oligomeric interactions of human voltage‐dependent anion channel 1 下载免费PDF全文
Toshiaki Hosaka Masateru Okazaki Tomomi Kimura‐Someya Yoshiko Ishizuka‐Katsura Kaori Ito Shigeyuki Yokoyama Kosuke Dodo Mikiko Sodeoka Mikako Shirouzu 《Protein science : a publication of the Protein Society》2017,26(9):1749-1758
Voltage‐dependent anion channel 1 (VDAC1), which is located in the outer mitochondrial membrane, plays important roles in various cellular processes. For example, oligomerization of VDAC1 is involved in the release of cytochrome c to the cytoplasm, leading to apoptosis. However, it is unknown how VDAC1 oligomerization occurs in the membrane. In the present study, we determined high‐resolution crystal structures of oligomeric human VDAC1 (hVDAC1) prepared by using an Escherichia coli cell‐free protein synthesis system, which avoided the need for denaturation and refolding of the protein. Broad‐range screening using a bicelle crystallization method produced crystals in space groups C222 and P22121, which diffracted to a resolution of 3.10 and 3.15 Å, respectively. Each crystal contained two hVDAC1 protomers in the asymmetric unit. Dimer within the asymmetrical unit of the crystal in space group C222 were oriented parallel, whereas those of the crystal in space group P22121 were oriented anti‐parallel. From a model of the crystal in space group C222, which we constructed by using crystal symmetry operators, a heptameric structure with eight patterns of interaction between protomers, including hydrophobic interactions with β‐strands, hydrophilic interactions with loop regions, and protein–lipid interactions, was observed. It is possible that by having multiple patterns of interaction, VDAC1 can form homo‐ or hetero‐oligomers not only with other VDAC1 protomers but also with other proteins such as VDAC2, VDAC3 and apoptosis‐regulating proteins in the Bcl‐2 family. 相似文献
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Okajima F Kurihara M Ono C Nakajima Y Tanimura K Sugihara H Tatsuguchi A Nakagawa K Miyazawa T Oikawa S 《Biochimica et biophysica acta》2005,1687(1-3):173-180
We examined the effect of oxidized low-density lipoprotein (oxLDL) on the insulin secretion in the culture of HIT-T15 cell line, an islet beta-cell line derived from a hamster pancreatic tumor. In order to check the uptake of modified LDL by HIT-T15 cells, we prepared DiI-labeled native LDL (nLDL), acetylated LDL (AcLDL), and oxLDL. After the addition of each LDL into the cultures of HIT-T15 cells, fluorescence microscopic study was done. It was suggested that AcLDL and oxLDL were taken up by HIT-T15 cells, as well as nLDL. mRNA expression of the LDL receptor, CD36, and SR-B1 was detected in HIT-T15 by RT-PCR. The medium insulin level was measured in the culture of HIT-T15 cells with each LDL. oxLDL significantly reduced the insulin secretion stimulated by various concentrations of glucose, the intracellular content of insulin, and the expression of preproinsulin mRNA compared to the control cultures without LDL addition. In contrast, nLDL and AcLDL had no effect on the insulin secretion, the intracellular insulin level, or the expression of preproinsulin mRNA. MTT assay findings (reflecting cell numbers) were not different between cultures with and without LDLs. These results indicated that oxLDL disturbed the insulin metabolism of HIT-T15 cells. 相似文献
46.
Kawasaki M Fujino M Li XK Kitazawa Y Funeshima N Takahashi R Ueda M Amano T Hakamata Y Kobayashi E 《Biochemical and biophysical research communications》2003,311(4):920-928
Suicide gene expression in specific tissue of transgenic animals has been used for cell-specific ablation. To examine the influence of hepatocyte removal, we produced the herpes simplex virus thymidine kinase (HSVtk) transgenic rat, whose gene was regulated by an albumin enhancer promoter. The liver presence of HSVtk was demonstrated in one line of the transgenic rats. We injected ganciclovir (GCV, 50mg/kg) into the rat on alternate days. After 28 days of GCV administration, liver tissues, and blood of the rats were collected. The histological investigation revealed infiltration of T cells, macrophages, granulocytes/neutrophils, and hepatocyte cell death. The biochemistry analysis demonstrated elevated levels of AST, ALT, and total bilirubin in transgenic rat. In conclusion, the transgenic rat with expressed albumin-specific HSVtk developed experimental hepatitis with administration of GCV, and will be a useful model to facilitate the evaluation of drug effects for clinical control of liver disease. 相似文献
47.
Ikeda M Umami K Hinohara M Tanimura Y Ohmae A Nakanishi Y Maeshima M 《Journal of experimental botany》2002,53(378):2273-2275
The function of the translation product of cDNA for Acetabularia vacuolar H(+)-pyrophosphatase was examined using the Saccharomyces cerevisiae VMA3-deficient strain. The open reading frame of Acetabularia H(+)-pyrophosphatase was revealed to encode 751 amino acids (721 or 751 amino acids in a previous paper). The acidification of the vacuole was observed by fluorescence microscopy when the cDNA was constructed in pYES2. Immunoblot analysis also supported the localization of the translation product in the vacuolar-membrane-enriched fraction. 相似文献
48.
Sasamura T Sasaki N Miyashita F Nakao S Ishikawa HO Ito M Kitagawa M Harigaya K Spana E Bilder D Perrimon N Matsuno K 《Development (Cambridge, England)》2003,130(20):4785-4795
Notch signalling, which is highly conserved from nematodes to mammals, plays crucial roles in many developmental processes. In the Drosophila embryo, deficiency in Notch signalling results in neural hyperplasia, commonly referred to as the neurogenic phenotype. We identify a novel maternal neurogenic gene, neurotic, and show that it is essential for Notch signalling. neurotic encodes a Drosophila homolog of mammalian GDP-fucose protein O-fucosyltransferase, which adds fucose sugar to epidermal growth factor-like repeats and is known to play a crucial role in Notch signalling. neurotic functions in a cell-autonomous manner, and genetic epistasis tests reveal that Neurotic is required for the activity of the full-length but not an activated form of Notch. Further, we show that neurotic is required for Fringe activity, which encodes a fucose-specific beta1, 3 N-acetylglucosaminyltransferase, previously shown to modulate Notch receptor activity. Finally, Neurotic is essential for the physical interaction of Notch with its ligand Delta, and for the ability of Fringe to modulate this interaction in Drosophila cultured cells. We present an unprecedented example of an absolute requirement of a protein glycosylation event for a ligand-receptor interaction. Our results suggest that O-fucosylation catalysed by Neurotic is also involved in the Fringe-independent activities of Notch and may provide a novel on-off mechanism that regulates ligand-receptor interactions. 相似文献
49.
Yusuke Mizokami Ko Noguchi Mikiko Kojima Hitoshi Sakakibara Ichiro Terashima 《Plant, cell & environment》2019,42(4):1257-1269
C3 photosynthesis is often limited by CO2 diffusivity or stomatal (gs) and mesophyll (gm) conductances. To characterize effects of stomatal closure induced by either high CO2 or abscisic acid (ABA) application on gm, we examined gs and gm in the wild type (Col‐0) and ost1 and slac1‐2 mutants of Arabidopsis thaliana grown at 390 or 780 μmol mol?1 CO2. Stomata of these mutants were reported to be insensitive to both high CO2 and ABA. When the ambient CO2 increased instantaneously, gm decreased in all these plants, whereas gs in ost1 and slac1‐2 was unchanged. Therefore, the decrease in gm in response to high CO2 occurred irrespective of the responses of gs. gm was mainly determined by the instantaneous CO2 concentration during the measurement and not markedly by the CO2 concentration during the growth. Exogenous application of ABA to Col‐0 caused the decrease in the intercellular CO2 concentration (Ci). With the decrease in Ci, gm did not increase but decreased, indicating that the response of gm to CO2 and that to ABA are differently regulated and that ABA content in the leaves plays an important role in the regulation of gm. 相似文献
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