研究者詳細 - 木下　専

論文 - 木下　専

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Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter 査読有り

Ihara M, Tomimoto H, Kinoshita M, Oh J, Noda M, Wakita H, Akiguchi I, Shibasaki H

Journal of Cerebral Blood Flow and Metabolism 21 巻頁： 828-834 2001年

Roles of Septins in the Mammalian Cytokinesis Machinery 査読有り

Makoto Kinoshita, Makoto Noda

Cell Structure and Function 26 巻 ( 6 ) 頁： 667 - 670 2001年

Phosphorylation of a New Brain-specific Septin, G-septin, by cGMP-dependent Protein Kinase 査読有り国際共著

Jing Xue, Xin Wang, Chandra S. Malladi, Makoto Kinoshita, Peter J. Milburn, Imre Lengyel, John A. P. Rostas, Phillip J. Robinson

Journal of Biological Chemistry 275 巻 ( 14 ) 頁： 10047 - 10056 2000年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Society for Biochemistry {\&} Molecular Biology ({ASBMB})

The septins are a family of GTPase enzymes, some of which are required for the cytokinesis stage of cell di vision and others of which are associated with exocytosis. me purified and cloned the cDNA for a 40-kDa protein from rat brain that is a substrate for type I cGMP-dependent protein kinase (PKG). The amino acid sequences of two tryptic peptides of P40 showed high homology to the septins. Molecular cloning revealed the 358-amino acid P40 to be a new member of the septin family. P40 was named G-septin, as it is phosphorylated in, vitro by PKG, but relatively poorly by the related cAMP dependent protein kinase and not by protein kinase C, Two splice variants of G-septin (alpha and beta) were found with distinct N and C termini, but a common GTPase domain. G-septin lacks the C-terminal coiled-coil domain characteristic of all other mammalian septins and uniquely has two predicted phosphorylation site motifs for type I PKG. Photoaffinity labeling with [alpha-P-32]GTP confirmed that G-septin is a GTP-binding protein. Northern blotting showed that G-septin mRNA (5.0 kilobases) is highly expressed in brain and undetectable in 12 other tissues, indicating that the G-septins are primarily neuronal proteins. Very low levels of 6.0-, 3.4-, and 2.6-kilobase transcripts were found in testis. Our results reveal a new class of brain-specific septins that may be regulated by PKG in neurons.

DOI： 10.1074/jbc.275.14.10047

Web of Science

PubMed

Differential localization of septins in the mouse brain 査読有り

Ayae Kinoshita, Makoto Noda, Makoto Kinoshita

Journal of Comparative Neurology 428 巻 ( 2 ) 頁： 223 - 239 2000年

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley-Blackwell

We have carried out a comparative immunohistochemical study on four members of the septin family, CDCrel-1, Septin6, CDC10, and H5, which are abundantly expressed in the adult mouse brain. We found that each septin showed overlapping but distinct distribution at the levels of light and electron microscopy. CDCrel-1 was abundant in inhibitory presynaptic terminals and associated with GABAergic vesicles in the thalamus, globus pallidus, and cerebellar nuclei. Septin6 was associated with synaptic vesicles in various brain regions, including glomeruli of the olfactory bulb. CDC10 was diffusely expressed in the brain and was localized beneath presynaptic membrane and astroglial processes. H5 was localized in the astroglial processes in some specific brain regions. The differential expression and subcellular localization of these septins indicates that a given neuron or glial cell expresses a specific set of septin monomers and that the resulting septin complexes with distinct compositions may play distinct roles in the brain. (C) 2000 Wiley-Liss, Inc.

DOI： 10.1002/1096-9861(20001211)428:2<223::aid-cne3>3.0.co;2-m

Web of Science

PubMed

Identification of Septins in Neurofibrillary Tangles in Alzheimer's Disease 査読有り

Ayae Kinoshita, Makoto Kinoshita, Haruhiko Akiyama, Hidekazu Tomimoto, Ichiro Akiguchi, Sharad Kumar, Makoto Noda, Jun Kimura

The American Journal of Pathology 153 巻 ( 5 ) 頁： 1551 - 1560 1998年11月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier {BV}

Septins are evolutionarily conserved cytoskeletal GTPases that can form heteropolymer complexes involved hi cytokinesis and other cellular processes. We detected expression of the human septin genes Nedd5, H5, Diff6, and hCDC10 in postmortem brain tissues using the reverse transcription-coupled polymerase chain reaction and their products by immunoblot analysis, Four antibodies directed against three septins, Nedd5, H5, and Diff6, consistently labeled neurofibrillary tangles, neuropil threads, and dystrophic neurites in the senile plaques in brains affected by Alzheimer's disease but did not label obvious structures in young control brains. Immunoelectron microscopy revealed that Nedd5 localized to the paired helical filaments, Pre-tangles, the precursory granular deposits that accumulate in the neuronal cytoplasm, also were labeled with the antibodies. These findings suggest that at least the three septins are associated with tau-based paired helical filament core, and may contribute to the formation of neurofibrillary tangle as integral constitutents of paired helical filaments.

DOI： 10.1016/s0002-9440(10)65743-4

Web of Science

PubMed

Caspases in Cell Death 査読有り国際共著

Loretta Dorstyn, Makoto Kinoshita, Sharad Kumar

Results and Problems in Cell Differentiation 24 巻頁： 1 - 24 1998年

cDNA Cloning, Expression Analysis, and Mapping of the MouseNedd4Gene 査読有り国際共著

Sharad Kumar, Kieran F. Harvey, Makoto Kinoshita, Neal G. Copeland, Makoto Noda, Nancy A. Jenkins

Genomics 44 巻 ( 1 ) 頁： 156 - 156 1997年8月

A novel gene encoding a ferredoxin reductase-like protein expressed in the neuroectoderm in Xenopus neurula 査読有り

Seigo Hatada, Makoto Kinoshita, Hirofumi Sakumoto, Reina Nishihara, Makoto Noda, Makoto Asashima

Gene 194 巻 ( 2 ) 頁： 297 - 299 1997年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier {BV}

In an attempt to elucidate the molecular mechanisms of early neural development in Xenopus laevis, we identified, using a differential display method, several genes that are induced after Concanavalin A treatment in the animal caps prepared from stage 9 blastula. One such gene was found to encode a possible type IIIa membrane protein of 66.2 kDa sharing similarities with several prokaryotic and eukaryotic redox enzymes, hence the putative product was named Nfrl, neurula-specific ferredoxin reductase-like protein. Northern blot analysis confirmed that the expression of the Nfrl gene is up-regulated around the neurula stage, and is much lower in embryos of earlier stages and in adult tissues. The temporally limited expression of this gene implies neurula- and early larva-specific redox reactions of certain substrates, the nature of which remains to be elucidated. (C) 1997 Elsevier Science B.V.

DOI： 10.1016/s0378-1119(97)00208-4

Web of Science

Nedd5, a mammalian septin, is a novel cytoskeletal component interacting with actin-based structures 査読有り国際共著

M Kinoshita, S Kumar, A Mizoguchi, C Ide, A Kinoshita, T Haraguchi, Y Hiraoka, M Noda

Genes & Development 11 巻 ( 12 ) 頁： 1535 - 1547 1997年6月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：COLD SPRING HARBOR LAB PRESS

The mouse Nedd5 gene encodes a 41.5-kD GTPase similar to the Saccharomyces and Drosophila septins essential for cytokinesis. Nedd5 accumulates near the contractile ring from anaphase through telophase, and finally condenses into the midbody. Microinjection of anti-Nedd5 antibody interferes with cytokinesis, giving rise to binucleated cells. In interphase and postmitotic cells, Nedd5 localizes to fibrous or granular structures depending on the growth state of the cell. The Nedd5-containing fibers are disrupted by microinjection of GTP gamma S and by Nedd5 mutants lacking GTP-binding activity, implying that GTP hydrolysis is required for its assembly. The Nedd5-containing fibers also appear to physically contact actin bundles and focal adhesion complexes and are disrupted by cytochalasin D, C3 exoenzyme, and serum starvation, suggesting a functional interaction with the actin-based cytoskeletal systems in interphase cells.

DOI： 10.1101/gad.11.12.1535

Web of Science

PubMed

Up-Regulation of the Nedd2 Gene Encoding an ICE/Ced-3-Like Cysteine Protease in the Gerbil Brain After Transient Global Ischemia 査読有り国際共著

Makoto Kinoshita, Hidekazu Tomimoto, Ayae Kinoshita, Sharad Kumar, Makoto Noda

Journal of Cerebral Blood Flow & Metabolism 17 巻 ( 5 ) 頁： 507 - 514 1997年5月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature Publishing Group

We assessed the expression of several genes encoding pro-apoptotic cysteine proteases similar to interleukin-1 beta converting enzyme (ICE) and nematode Ced-3 in association with delayed neuronal death (DND) after transient forebrain ischemia in Mongolian gerbil. The levels of the two species of Nedd2 mRNA concomitantly increased about twofold in the whole forebrain at 3-6 h after 10-min ischemia and declined to the basal level by 24 h. In situ hybridization revealed that the Nedd2 gene was up-regulated in some neuronal populations in CA(1) and CA(3) regions of the hippocampus. In contrast, expression of ICE, CPP32/Yama/Apopain, and TX/ICErelII did not change within 48 h. These observations raise the possibility that up-regulation of Nedd2 in the vulnerable neurons may contribute to the proteolytic processes preceding the manifestation of apoptosis and/or necrosis after ischemic insult.

DOI： 10.1097/00004647-199705000-00004

Web of Science

PubMed

Characterization of a mammalian cell death gene Nedd2 査読有り国際共著

Kumar S, Kinoshita M, Noda M

Leukemia 11 Suppl 3 巻頁： 385 - 386 1997年4月

cDNA Cloning, Expression Analysis, and Mapping of the Mouse Nedd4 Gene 査読有り国際共著

Sharad Kumar, Kieran F. Harvey, Makoto Kinoshita, Neal G. Copeland, Makoto Noda, Nancy A. Jenkins

Genomics 40 巻 ( 3 ) 頁： 435 - 443 1997年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier {BV}

The Nedd4 gene was initially identified by a subtraction cloning approach as a highly expressed transcript in the mouse embryonic brain. Cloning of the Nedd4 cDNA indicated that it can encode a protein of approximately 103 kDa, consisting of a Ca2+ and phospholipid binding domain, three putative protein-protein interaction domains (the WW domains), and a carboxyl-terminus region similar to the ubiquitin-protein ligase domain (hect domain). In mouse embryos, the expression of Nedd4 in the central nervous system is highest during neurogenesis and decreases as development progresses. In addition to the central nervous system, the expression of Nedd4 is detected in various embryonic tissues and persists in most adult tissues. Using an antibody raised against a fusion protein, we show that Nedd4 protein is localized to the cellular cytoplasm. We have mapped the mouse Nedd4 gene to chromosome 9 using an interspecific backcross panel. Nedd4 maps to a previously defined homologous region between human and mouse chromosomes and thus provides additional information regarding interspecies comparative mapping. (C) 1997 Academic Press.

DOI： 10.1006/geno.1996.4582

Web of Science

Origin, expression and possible functions of the two alternatively spliced forms of the mouse Nedd2 mRNA. 査読有り国際共著

Kumar S, Kinoshita M, Dorstyn L, Noda M

Cell Death and Differentiation 4 巻頁： 378-387 1997年

An interferon regulatory factor-related gene (xIRF-6) is expressed in the posterior mesoderm during the early development of Xenopus laevis 査読有り

Seigo Hatada, Makoto Kinoshita, Shuji Takahashi, Reina Nishihara, Hirofumi Sakumoto, Akimasa Fukui, Makoto Noda, Makoto Asashima

Gene 203 巻 ( 2 ) 頁： 183 - 188 1997年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier {BV}

Out of a Xenopus neurula cDNA library, we isolated a clone which encodes a 52.4-kDa protein highly similar to the mouse interferon regulatory factor, IRF-6, whose function is unknown. The mRNA of this gene, named xIRF-6, seems to be maternally transmitted, but its amount rapidly decreases after the tailbud stage. Whole-mount in situ hybridization showed that xIRF-6 mRNA is expressed in the presumptive semitic mesoderm in the late gastrula, and then confined to a segment of posterior somite during the neurula through the tailbud stage. The temporally and spatially limited expression of the xIRF-6 gene product may contribute to the transcriptional regulation of specific genes which are necessary for the development of the posterior somites. (C) 1997 Elsevier Science B.V.

DOI： 10.1016/s0378-1119(97)00512-x

Web of Science

Origin, expression and possible functions of the two alternatively spliced forms of the mouse Nedd2 mRNA 査読有り

Sharad Kumar, Makoto Kinoshita, Loretta Dorstyn, Makoto Noda

Cell Death and Differentiation 4 巻 ( 5 ) 頁： 378 - 387 1997年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature Publishing Group

The Nedd2 gene, a member of the ICE/ced-3 family, transcribes two mRNA species by differential splicing. One of these encodes a shorter truncated version of the protein termed Nedd2s/ICH-1s. While Nedd2/ICH-1 induces apoptosis, ICH-1s was proposed to be a negative regulator of cell death. In this communication we have analyzed various aspects of the Nedd2s/ICH-1s. The coding region of mouse Nedd2 consists of 10 exons and alternative splicing of the 7th exon results in the generation of two transcripts. Although Nedd2s expression conferred partial resistance to serum withdrawal-induced apoptosis in NIH-3T3 cells, it failed to prevent cell death induced by the overexpression of Nedd2 and was unable to suppress apoptosis in two other cell lines (N18 and FDC-P1) under factor deprived conditions. Our results indicate that Nedd2s/ICH-1s is not a general modulator of cell death.

DOI： 10.1038/sj.cdd.4400251

Web of Science

Caspase-2/Nedd2/Ich-1 招待有り査読有り

木下　専、野田　亮

アポトーシス (Bio Science用語ライブラリー) 頁： 105 - 106 1996年12月

Identification of a Xenopus glutamine synthetase gene abundantly expressed in the embryonic nervous system but not in adult brain 査読有り

Seigo Hatada, Makoto Kinoshita, Makoto Noda, Makoto Asashima

FEBS Letters 371 巻 ( 3 ) 頁： 287 - 292 1995年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier {BV}

We used a PCR-based subtraction cloning procedure with concanavalin A-treated and -untreated animal caps from stage 9 Xenopus embryos to search for genes up-regulated during early neural development. One such gene was found to encode a protein homologous to several known glutamine synthetases, and we named it xGS, Molecular hybridization studies revealed that xGS mRNA is maternally transmitted and abundantly expressed in neuroectoderm-derived tissues during the gastrula and neurula stages, The expression of xGS mRNA in the nervous system continues until the larval stages, but declines thereafter and becomes undetectable in adult brain, Considering its metabolic activity and potential neuroprotective effect against the neurotoxic substances such as glutamate and ammonia, the glutamine synthetase may play an important role in the early stages of vertebrate neural development.

DOI： 10.1016/0014-5793(95)00913-t

Web of Science

HMG-X, a Xenopus gene encoding an HMG1 homolog, is abundantly expressed in the developing nervous system 査読有り

FEBS Letters 352 巻 ( 2 ) 頁： 191 - 196 1994年9月

Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme 査読有り国際共著

S Kumar, M Kinoshita, M Noda, N G Copeland, N A Jenkins

Genes & Development 8 巻 ( 14 ) 頁： 1613 - 1626 1994年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：COLD SPRING HARBOR LAB PRESS

By subtraction cloning we previously identified a set of mouse genes (named Nedd1 through Nedd10) with developmentally down-regulated expression in brain. We now show that one such gene, Nedd2, encodes a protein similar to the mammalian interleukin-1 beta-converting enzyme (ICE) and the product of the Caenorhabditis elegans cell death gene ced-3 (CED-3). Both ICE and CED-3 are known to encode putative cysteine proteases and induce apoptosis when overexpressed in cultured cells. Overexpression of Nedd2 in cultured fibroblast and neuroblastoma cells also resulted in cell death by apoptosis, which was suppressed by the expression of the human bcl-2 gene, indicating that Nedd2 is functionally similar to the ced-3 gene in C. elegans. We also show that during embryonic development, Nedd2 is highly expressed in several types of mouse tissue undergoing high rates of programmed cell death such as central nervous system and kidney. Our data suggest that Nedd2 is an important component of the mammalian programmed cell death machinery.

DOI： 10.1101/gad.8.14.1613

Web of Science

PubMed

Vector Analysis of Corneal Astigmatism after Scleral Buckling Surgery 査読有り

Makoto Kinoshita, Hidenobu Tanihara, Akira Negi, Shin-Ichiro Kawano, Hitoshi Ishigouoka, Yoshiki Veda, Satomi Suzuki-Yoshida, Yoshihito Honda

Ophthalmologica 208 巻 ( 5 ) 頁： 250 - 253 1994年

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：S. Karger {AG}

We conducted a short-term prospective study of 125 eyes with retinal detachment to examine changes of corneal astigmatism about 2 weeks after scleral buckling surgery, using a vector method on 2-fold-angle rectangular coordinates. Segmental buckles of one to less than two quadrants produced significantly greater changes in astigmatism (1.65+/-0.97 dptr) than those of less than one quadrant (0.88+/-0.75 dptr) and those spanning two quadrants or more (1.09+/-0.38 dptr) (p=0.0005, Kruskal-wallis test; n=73). The amplitude of differential vectors after explant buckling surgery (1.33+/-0.89 dptr, n=24) was significantly greater than after implant buckling surgery (0.65+/-0.45 dptr, n=15) (p=0.009, Mann-Whitney U-test) with buckles of one quadrant or less. Differential vectors tended to direct toward the buckles. There was no obvious directional tendency in the case of encircling procedures (n=52).

DOI： 10.1159/000310501

Web of Science

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