Yoshihide Ohe

Publications (7)16.81 Total impact

• Article: A large form of secretogranin III functions as a sorting receptor for chromogranin A aggregates in PC12 cells.

  Lu Han, Masayuki Suda, Keisuke Tsuzuki, Rong Wang, Yoshihide Ohe, Hirokazu Hirai, Tsuyoshi Watanabe, Toshiyuki Takeuchi, Masahiro Hosaka
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  ABSTRACT: Granin-family proteins, including chromogranin A and secretogranin III, are sorted to the secretory granules in neuroendocrine cells. We previously demonstrated that secretogranin III binds chromogranin A and targets it to the secretory granules in pituitary corticotrope-derived AtT-20 cells. However, secretogranin III has not been identified in adrenal chromaffin and PC12 cells, where chromogranin A is correctly sorted to the secretory granules. In this study, low levels of a large and noncleaved secretogranin III have been identified in PC12 cells and rat adrenal glands. Although the secretogranin III expression was limited in PC12 cells, when the FLAG-tagged secretogranin III lacking the secretory granule membrane-binding domain was expressed excessively, hemagglutinin-tagged chromogranin A was unable to target to the secretory granules at the tips and shifted to the constitutive secretory pathway. Secretogranin III was able to bind the aggregated form of chromogranin A, suggesting that a small quantity of secretogranin III is enough to carry a large quantity of chromogranin A. Furthermore, secretogranin III bound adrenomedullin, a major peptide hormone in chromaffin cells. Indeed, small interfering RNA-directed secretogranin III depletion impaired intracellular retention of chromogranin A and adrenomedullin, suggesting that they are constitutively released to the medium. We suggest that the sorting function of secretogranin III for chromogranin A is common in PC12 and chromaffin cells as well as in other endocrine cells, and a small amount of secretogranin III is able to sort chromogranin A aggregates together with adrenomedullin to secretory granules.
  Molecular Endocrinology 06/2008; 22(8):1935-49. · 4.54 Impact Factor
• Article: Ectodomain shedding of SHPS-1 and its role in regulation of cell migration.

  Hiroshi Ohnishi, Hisae Kobayashi, Hideki Okazawa, Yoshihide Ohe, Kyoko Tomizawa, Ryuji Sato, Takashi Matozaki
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  ABSTRACT: SHPS-1 is a transmembrane protein whose cytoplasmic region undergoes tyrosine phosphorylation and then binds the protein-tyrosine phosphatase SHP-2. Formation of the SHPS-1-SHP-2 complex is implicated in regulation of cell migration. In addition, SHPS-1 and its ligand CD47 constitute an intercellular recognition system that contributes to inhibition of cell migration by cell-cell contact. The ectodomain of SHPS-1 has now been shown to be shed from cells in a reaction likely mediated by a metalloproteinase. This process was promoted by activation of protein kinase C or of Ras, and the released ectodomain exhibited minimal CD47-binding activity. Metalloproteinases catalyzed the cleavage of a recombinant SHPS-1-Fc fusion protein in vitro, and the primary cleavage site was localized to the juxtamembrane region of SHPS-1. Forced expression of an SHPS-1 mutant resistant to ectodomain shedding impaired cell migration, cell spreading, and reorganization of the actin cytoskeleton. It also increased the tyrosine phosphorylation of paxillin and FAK triggered by cell adhesion. These results suggest that shedding of the ectodomain of SHPS-1 plays an important role in regulation of cell migration and spreading by this protein.
  Journal of Biological Chemistry 08/2004; 279(27):27878-87. · 4.77 Impact Factor
• Article: Effects of interleukin-1beta and prostaglandin E2 on prostaglandin D synthase production in cultivated rat leptomeningeal cells.

  Takeshi Muraki, Ko Fujimori, Mami Ishizaka, Yoshihide Ohe, Yoshihiro Urade, Fumikazu Okajima, Koichi Ishikawa
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  ABSTRACT: Although the interleukin (IL)-1 receptor is densely distributed in the leptomeninges constituting the blood/cerebrospinal fluid barrier, its physiologic significance has remained unclear. In the present study, we show that in cultured leptomeningeal cells, IL-1beta, tumor necrosis factors, or lipopolysaccharide causes a prominent increase in the synthesis and release of prostaglandin (PG) D synthase, which catalyzes the final step in the biosynthesis of PGD2. Although significant increases in the amount of PGD synthase were also observed with cells exposed to somatostatin, thrombin, or ciliary neurotrophic factor, these were much smaller than were those induced by the proinflammatory cytokines. Other agents tested including IGF-I had no effect upon the enzyme levels in the culture media. Furthermore, we found that the increased secretion of PGD synthase by IL-1beta was completely inhibited by 10(-7) M PGE2. The same dose of PGD2 or 15-deoxy-Delta(12-14)PGJ2 had no effect upon the IL-1beta action. In addition, PGE2 increased the level of fibronectin and eliminated the expression of zonula occludentes-1, a tight junction-associated protein from cultured cells, effects likely reflecting a loss of barrier integrity. These results demonstrate the importance of inflammatory stimuli as a physiologic regulator of the leptomeningeal cell function.
  Journal of Cerebral Blood Flow &#38 Metabolism 05/2004; 24(4):409-18. · 5.01 Impact Factor
• Article: Characterization of nucleotide pyrophosphatase-5 as an oligomannosidic glycoprotein in rat brain.

  Yoshihide Ohe, Hiroshi Ohnishi, Hideki Okazawa, Kyoko Tomizawa, Hisae Kobayashi, Katsuya Okawa, Takashi Matozaki
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  ABSTRACT: Membrane glycoproteins of neural cells play crucial roles in axon guidance, synaptogenesis, and neuronal transmission. We have here characterized membrane glycoproteins containing terminal alpha-mannose residues in rat brain membranes. Affinity purification using Galanthus nivalis agglutinin, that is highly specific for terminal alpha-mannose residues, revealed a 50-kDa protein as well as 80-kDa SHPS-1 and 45-kDa beta2 subunit of Na,K-ATPase in rat brain membranes. Combination of N-terminal peptide sequencing and mass spectrometry indicated that the 50-kDa protein was rat nucleotide pyrophosphatase-5 (NPP-5). In contrast to other NPPs, NPP-5 was a type-I transmembrane protein. Northern blot analysis showed that NPP-5 was highly expressed in brain, but also expressed in other peripheral tissues. However, we could not detect either the NPP activity or the lysophospholipase D activity in the immunoprecipitates with antibodies to NPP-5 from rat brain membranes. These data, therefore, suggest that NPP-5 is a neural oligomannosidic glycoprotein that may participate in neural cell communications.
  Biochemical and Biophysical Research Communications 10/2003; 308(4):719-25. · 2.48 Impact Factor
• Article: Synthesis and secretion of insulin-like growth factor (IGF)-II and IGF binding protein-2 by cultivated brain meningeal cells

  Koichi Ishikawa, Yoshihide Ohe, Kazuhiko Tatemoto
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  ABSTRACT: The meninges (the pia mater and the arachnoid) covering the surface of brain parenchyma are known to participate in the regulation of blood circulation and the blood-cerebrospinal fluid barrier. In the present study, we isolated and characterized some of the major proteins secreted into the conditioned medium of the meningeal cell cultures prepared from 1–2-day-old rats. Five protein molecules (7 kDa, 16 kDa, 18 kDa, 27 kDa and 32 kDa) were recognized as major proteins in the conditioned medium by SDS-PAGE. The major proteins were isolated and purified to homogeneity, respectively. Their N-terminal sequences, except that of 27 kDa protein, were successfully determined. Homology search has revealed that the N-terminal sequences of the 7 kDa protein and the 32 kDa protein were identical with those of insulin-like growth factor-II (IGF-II) and IGF-binding protein-2 (IGFBP-2), respectively. The N-terminal sequences of the 16 kDa and 18 kDa molecules were identical with those of the corresponding fragments of IGFBP-2. The present study demonstrates that cultured meningeal cells produce and secrete large amounts of IGF-II and IGFBP-2. The meninges may, therefore, be one of the main sources of these proteins in the cerebrospinal fluid and involved in the modulation of neuronal and/or glial cell survival or functioning.
  Brain Research.
• Article: Activation of iron handling system within the gerbil hippocampus after cerebral ischemia

  Hirohisa Ishimaru, Koichi Ishikawa, Yoshihide Ohe, Akira Takahashi, Kazuhiko Tatemoto, Yuji Maruyama
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  ABSTRACT: Analyzing the distribution pattern of transferrin (Tf) and ferritin, we investigated the changes in iron metabolism related proteins in the process of neuronal death induced by 5 min ischemia. In the control animals, Tf immunoreactivity was localized in the oligodendrocytes. Ferritin was distributed in both neurons and gliacytes, particularly microglia. In parallel with the delayed neuronal death, Tf-positive atrophied neurons and numerous ferritin-positive gliacytes appeared in the CAI subfield of the hippocampus 4 days after ischemia, when glia fibrillary acidic protein (GFAP)-positive astrocytes also appeared throughout the hippocampal structure. A considerable number of ferritin-positive phagocytes (reactive microglia) appeared in the stratum pyramidale from the seventh day. Our data show clearly that the mobilization of Tf and ferritin-positive phagocytes are linked with the degeneration of neurons induced by cerebral ischemia. These events may suggest an activation of iron handling system under the postischemic condition.
  Brain Research.
• Article: Cystatin C and apolipoprotein E immunoreactivities in CA1 neurons in ischemic gerbil hippocampus

  Hirohisa Ishimaru, Koichi Ishikawa, Yoshihide Ohe, Akira Takahashi, Yuji Maruyama
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  ABSTRACT: The distribution patterns of cystatin C and apolipoprotein E (apo E) were studied immunocytochemically in the gerbil hippocampus before and after 5 min ischemia. In the controls, cystatin C was distributed mainly in astrocytes. In addition, a large number of dots positive for cystatin C were observed around the outlines of neuronal perikarya in the CA1 subfields. One day after ischemia, cystatin C-positive stainings outlining neuronal cell bodies disappeared. On the fourth day, intense stainings for cystatin C appeared in atrophied pyramidal neurons and these stainings in neurons disappeared by the 14th day. A remarkable increase in the number of cystatin C-positive astrocytes occurred on the fourth day and thereafter these spread over the whole of the CA1 subfield. Apo E was also distributed in astrocytes in the control specimens. From the fourth day, extra- and/or intracellular distribution of apo E-immunoreactivities was noted in the stratum pyramidale. Apo E-positive astrocytes disappeared transiently on the fourth day and then reappeared and increased remarkably by the 14th day. These findings indicate that cystatin C and apo E are involved in the degeneration process of brain neuronal cells.
  Brain Research.