Biomedical subjects

Emiko Suzuki

Publications and source records attributed to Emiko Suzuki.

11 recordsLinked to original sources

PubMed2005

The chromokinesin Kid is required for maintenance of proper metaphase spindle size.

The human chromokinesin Kid/kinesin-10, a plus end-directed microtubule (MT)-based motor with both microtubule- and DNA-binding domains, is required for proper chromosome alignment at the metaphase plate. Here, we performed RNA interference experiments to deplete endogenous Kid from HeLa cells and confirmed defects in metaphase chromosome arm alignment in Kid-depleted cells. In addition, we noted a shortening of the spindle length, resulting in a pole-to-pole distance only 80% of wild type. The spindle microtubule-bundles with which Kid normally colocalize became less robust. Rescue of the two Kid deficiency phenotypes-imprecise chromosome alignment at metaphase and shortened spindles- exhibited distinct requirements. Mutants lacking either the DNA-binding domain or the MT motor ATPase failed to rescue the former defect, whereas rescue of the shortened spindle phenotype required neither activity. Kid also exhibits microtubule bundling activity in vitro, and rescue of the shortened spindle phenotype and the bundling activity displayed similar domain requirements, except that rescue required a coiled-coil domain not needed for bundling. These results suggest that distinct from its role in chromosome movement, Kid contributes to spindle morphogenesis by mediating spindle microtubules stabilization.

Cell Nucleus↗

PubMed2005

The slender lobes gene, identified by retarded mushroom body development, is required for proper nucleolar organization in Drosophila.

The nucleolus dynamically alters its shape through the assembly and disassembly of a variety of nucleolar components in proliferating cells. While the nucleolus is known to function in vital cellular events, little is known about how its components are correctly assembled. Through the analysis of a Drosophila mutant that exhibits a reduced number of mushroom body (MB) neurons in the brain, we reveal that the slender lobes (sle) gene encodes a novel nuclear protein that affects nucleolar organization during development. In sle mutant neuroblasts, the nucleolus was packed more tightly, forming a dense sphere, and the nucleolar proteins fibrillarin and Nop60B were abnormally distributed in the interphase nucleolus. Moreover, another nucleolar marker, Aj1 antigen, was localized to the center of the nucleolus in a manner complementary to the Nop60B distribution, and also formed a large aggregate in the cytoplasm. While developmental defects were limited to a few tissues in sle mutants, including MBs and nurse cells, the altered organization of the nucleolar components were evident in most developing tissues. Therefore, we conclude that Sle is a general factor of nuclear architecture in Drosophila that is required for the correct organization of the nucleolus during development.

Animals↗

PubMed2005

Influence of cigarette smoke on the L-ascorbic acid metabolism and the activities of drug-metabolizing enzyme in rats.

This study clarified the influence of cigarette smoke on the L-ascorbic acid (AsA) metabolism and the activities of drug-metabolizing enzyme in rats. The test rats (group T) were exposed to weak sidestream smoke from cigarettes for 2 h, everyday for 57 days. AsA concentration in the tissues and excreted amount of AsA in urine of group T tended to be higher than those of control group (group C). The plasma AsA concentration and the activities of aniline hydroxylase and 7-ethoxycoumarin O-deethylase of group T were significantly higher than those of group C. There was no significant difference in the activity of UDP glucuronosyltransferase or in the liver cytochrome P-450 content between these two groups.

7-Alkoxycoumarin O-Dealkylase↗

PubMed2004

Drosophila glucosylceramide synthase: a negative regulator of cell death mediated by proapoptotic factors.

Glucosylceramide synthase (GlcT-1) catalyzes the formation of glucosylceramide (GlcCer), the core structure of major glycosphingolipids (GSLs), from ceramide and UDP-glucose. Ceramide and its metabolites, such as sphingosine-1-phosphate, are now known to be important mediators of apoptosis and cell survival. Recently, we have shown that GlcT-1 functions to regulate intracellular ceramide levels via glycosylation of ceramide. In this study, we employ the fruit fly Drosophila melanogaster as a model system for understanding the in vivo roles of GlcT-1. We isolated and characterized a GlcT-1 homologue (DGlcT-1) from Drosophila. When DGlcT-1 was expressed in GM-95 cells deficient in GSLs (because of the absence of GlcT-1 activity), these cells regained the ability to synthesize GSLs. Northern blot and in situ hybridization analyses revealed that the expression of DGlcT-1 mRNA was ubiquitous throughout development, suggesting that DGlcT-1 is important for development and differentiation. Indeed, RNA interference experiments demonstrated that the loss of GlcT-1 function enhances apoptotic cell death. Conversely, targeted expression of GlcT-1 partially rescued cell death caused by the proapoptotic factors Reaper and Grim, suggesting that ceramide generation might be one signal pathway that executes the cell death program. We also found that GlcT-1 localized not only in the Golgi apparatus but also in the perinuclear endoplasmic reticulum, providing the first visual evidence of GlcT-1 in membranes. These results indicate that GlcT-1 might down-regulate ceramide generated in these membranes.

Amino Acid Sequence↗

PubMed2004

Receptor assay-guided isolation of anti-GABAergic insecticidal alkaloids from a fungal culture.

The gamma-aminobutyric acid (GABA) receptor bears sites of action for insecticides. To discover GABA receptor-directed insecticides in natural products, fungal culture extracts were screened for their ability to inhibit specific binding of the radiolabeled noncompetitive antagonist [3H]1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane to housefly head membranes. The screening efforts led to the isolation of two alkaloids from Aspergillus terreus: PF1198A (alantrypinone) and PF1198B (serantrypinone), which had IC50 values of 0.34 and 2.1 microM, respectively, in this assay. These compounds were ca. 47-61-fold selective for housefly vs rat GABA receptors. Both compounds showed insecticidal activity against Myzus persicae in the range of 100-500 ppm. Binding assay-guided screening should provide significant opportunities for the identification of novel and selective insecticides.

Alkaloids↗

PubMed2004

A lysosomal tetraspanin associated with retinal degeneration identified via a genome-wide screen.

The Drosophila visual system has provided a model to study phototransduction and retinal degeneration. To identify new candidate proteins that contribute to these processes, we conducted a genome-wide screen for genes expressed predominately in the eye, using DNA microarrays. This screen appeared to be comprehensive as it led to the identification of all 22 eye-enriched genes previously shown to function in phototransduction or implicated in retinal degeneration. In addition, we identified 93 eye-enriched genes whose roles have not been previously defined. One of the eye-enriched genes encoded a member of a large family of transmembrane proteins, referred to as tetraspanins. We created a null mutation in the eye-enriched tetraspanin, Sunglasses (Sun), which resulted in light-induced retinal degeneration. We found that the Sun protein was distributed primarily in lysosomes, and functioned in a long-known but poorly understood phenomenon of light-induced degradation of rhodopsin. We propose that lysosomal tetraspanins in mammalian cells may also function in the downregulation of rhodopsin and other G-protein-coupled receptors, in response to intense or prolonged agonist stimulation.

Amino Acid Sequence↗

PubMed2004

[A constrictive pericarditis on oral steroid and immunosuppressant treated with bilateral anterolateral thoracotomy; report of a case].

A successful case of pericardiectomy without median sternotomy for an immunosuppressive 59-year-old man with constrictive pericarditis (CP) was reported. He had a history of invasive thymoma, myasthenia gravis and pure red cell aplasia, and he was on oral steroid and immunosuppressant. Pericardiectomy was performed by the approach of bilateral anterolateral thoracotomy to avoid troubles due to median sternotomy under immunosuppression, and there was no postoperative infection such as mediastinitis. Bilateral anterolateral thoracotomy was considered to be useful for immunosuppressive cases.

Anti-Inflammatory Agents↗

PubMed2003

The effect of cigarette smoke exposure and ascorbic acid intake on gene expression of antioxidant enzymes and other related enzymes in the livers and lungs of Shionogi rats with osteogenic disorders.

Cigarette smoking causes many chronic diseases but is a preventable risk factor in developing countries. However, it may be possible to relieve the smoke-induced damage by increasing the protective defense system. As vitamin C intake reduces smoking risk, it is recommended that smokers should take more vitamin C. However, the molecular mechanism of vitamin C intake on smokers has not been thoroughly investigated. We have found there to be suppression of smoke-induced cytochrome P-450 1A1 (CYP1A1) mRNA expression by high-dose ascorbic acid administration. Therefore, we surveyed other genes, the expressions of which were altered by the administration of high-dose ascorbic acid. As cigarette smoking increases oxidative stress, we investigated the effect on antioxidative enzyme expression. The osteogenic disorder Shionogi (ODS) rat, which lacks ascorbic acid synthesis enzyme, was administered either minimal amounts (4 mg/day, S4) or high-dose amounts (40 mg/day, S40) of ascorbic acid, and were exposed to cigarette smoke daily for 25 days. The effect on antioxidative enzymes mRNA expression in the liver was measured by competitive reverse transcription-polymerase chain reaction method (competitive RT-PCR). CuZn-superoxide dismutase (SOD), MnSOD, catalase and protein disulfide isomerase (PDI) were significantly decreased by high-dose ascorbic acid administration, and plasma glutathione peroxidase was also decreased, but not significantly. Cigarette smoke exposure slightly increased gene expression of PDI and catalase, but not significantly. The differently expressed 27 genes in the liver were found by differential display methods. From 27 genes, altered expression of plasma proteinase inhibitor, alpha-1-inhibitor III and CYP1A2 were confirmed by competitive RT-PCR. These results show that ascorbic acid intake influences gene expression of antioxidative enzymes, an ascorbic acid recycle enzyme, and xenobiotic metabolizing enzymes.

Animals↗

PubMed2003

Enantioselective fluorination mediated by N-fluoroammonium salts of cinchona alkaloids: first enantioselective synthesis of BMS-204352 (MaxiPost).

We have employed a cinchona alkaloid/Selectfluor-mediated enantioselective fluorination of the oxindole 2 to achieve the first enantioslective synthesis of BMS-204352 (MaxiPost, S-1), an effective opener of maxi-K channels. Fluorination occurred to produce S-1 with 84% ee using the bis-cinchona alkaloid (DHQ)(2)AQN. Recrystallization produced enantiomerically pure (>99% ee) product. Quinidine-mediated fluorination of 2 gave the (R)-antipode of 1 with 68% ee.

Catalysis↗

PubMed2002

Ebola virus VP40 drives the formation of virus-like filamentous particles along with GP.

Using biochemical assays, it has been demonstrated that expression of Ebola virus VP40 alone in mammalian cells induced production of particles with a density similar to that of virions. To determine the morphological properties of these particles, cells expressing VP40 and the particles released from the cells were examined by electron microscopy. VP40 induced budding from the plasma membrane of filamentous particles, which differed in length but had uniform diameters of approximately 65 nm. When the Ebola virus glycoprotein (GP) responsible for receptor binding and membrane fusion was expressed in cells, we found pleomorphic particles budding from the plasma membrane. By contrast, when GP was coexpressed with VP40, GP was found on the filamentous particles induced by VP40. These results demonstrated the central role of VP40 in formation of the filamentous structure of Ebola virions and may suggest an interaction between VP40 and GP in morphogenesis.

Cell Line↗

PubMed2002

[Study on difference in olfactory response in dysosmia patients].

Using 1952 dysosmia patients, we studied the difference in olfactory response to 5 types of odorous substances used in the standard olfactory acuity test in Japan--beta-phenyl ethyl alcohol, methyl cyclopentenolone, isovaleric acid, gamma-undecalactone, and scatol. Olfactory dysfunctions included 887 patients with chronic paranasal sinusitis, 255 with allergic rhinitis, 326 with common cold sequela, 77 with complications from head injuries, 28 with drug-induced dysosmia, 39 with congenital dysosmia, 257 with dysosmia of unknown etiology, and 83 miscellaneous. The standard olfactory acuity test before treatment indicated that 82 patients detected only one odor within the detection threshold and 157 within the recognition threshold; 40 responded only to isovaleric acid at the detection threshold and 101 at the recognition threshold. Both figures were significantly greater than those who responded to other odors (p < 0.01). No specific trends were noted in etiologies of dysosmia that allowed smelling of isovaleric acid only either at the detection or recognition threshold. Among those whose olfactory thresholds were judged to be scaled out against all 5 odorous substances, 552 were rated as scaled out at the detection threshold and 630 at the recognition threshold. During post treatment, 33 scaled out at the detection threshold and 32 scaled out at the recognition threshold improved enough to smell 1 type of odor. Of these, 15 scaled out at the detection threshold and 13 scaled out at the recognition threshold became able to smell only isovaleric acid. Those becoming able to smell only isovaleric acid either at the detection or recognition threshold, significantly outnumbered those becoming able to smell other odors (p < 0.01). No outstanding cause of dysosmia was seen in those able to smell isovaleric acid. This data indicates that olfactory function for detecting isovaleric acid is relatively resistant to disease and is most likely to be restored. The difference in olfactory response of patients with olfactory dysfunction such as those above may be due to variations in the number of olfactory receptor proteins for specific odors within olfactory cells or different responses to the type of molecules of odor-emitting substances.

Adolescent↗