Satoko Hanaka

Publications (6)12.08 Total impact

• Article: Transduction of phosphatase and tensin homolog deleted on chromosome 10 into eosinophils attenuates survival, chemotaxis, and airway inflammation.

  Tetsuya Adachi, Satoko Hanaka, Tomoko Masuda, Hisanao Yoshihara, Hiroyuki Nagase, Ken Ohta
  [show abstract] [hide abstract]
  ABSTRACT: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is part of a complex signaling system that affects a variety of important cell functions. PTEN antagonizes the action of PI3K by dephosphorylating the signaling lipid phosphatidylinositol 3,4,5-triphosphate. In the present study, we used a TAT fusion protein transduction system to elucidate the role of PTEN in eosinophils and airway inflammation. A small region of the HIV TAT protein (YGRKKRRQRRR), a protein transduction domain known to enter mammalian cells efficiently, was fused to the N terminus of PTEN. Flow cytometric analysis of annexin V- and propidium iodide-stained cells was used to assess eosinophil survival. A chemotaxis assay was performed using a Boyden chamber. Cell analysis in bronchoalveolar lavage fluid and histological examinations were performed using OVA-challenged A/J mice. We found that TAT-PTEN was successfully internalized into eosinophils and functioned as a phosphatase in situ. TAT-PTEN, but not a TAT-GFP control protein, blocked the ability of IL-5 to prevent the apoptosis of eosinophils from allergic subjects. The eotaxin-induced eosinophil chemotaxis was inhibited by TAT-PTEN in a dose-dependent manner. Intranasal pretreatment with TAT-PTEN, but not TAT-GFP, significantly inhibited the OVA-induced eosinophil infiltration in bronchoalveolar lavage fluid. Histological examination of the lung, including H&E and Alcian blue/periodic acid-Schiff staining, revealed that TAT-PTEN, but not TAT-GFP, abrogated eosinophilic inflammation and mucus production. Our results suggest that PTEN negatively regulates eosinophil survival, chemotaxis, and allergic inflammation. The pharmacological targeting of PTEN may constitute a new strategy for the treatment of eosinophilic disorders.
  The Journal of Immunology 12/2007; 179(12):8105-11. · 5.79 Impact Factor
• Article: The role of platelet-derived growth factor receptor in eotaxin signaling of eosinophils.

  Tetsuya Adachi, Satoko Hanaka, Tomoko Yano, Koichi Yamamura, Hisanao Yoshihara, Hiroyuki Nagase, Junichi Chihara, Ken Ohta
  [show abstract] [hide abstract]
  ABSTRACT: Receptor tyrosine kinases (RTKs) such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR) are capable of eliciting kinase activity after ligand binding. In several cells, RTKs are activated via the G-protein-coupled receptor independent of the ligand-RTK interaction. We have previously found that EGFR is transactivated via CC chemokine receptor 3 in bronchial epithelial cells and that this pathway is important for mitogen-activated protein (MAP) kinase activation and cytokine production. It has recently been suggested that hypereosinophilic syndrome results from the fusion tyrosine kinase FIP1L1-PDGFRA. Although it is possible that the PDGFR signal is involved in eosinophil function, the details are still unclear. Blood eosinophils were purified using Percoll and anti-CD16 antibody-coated magnetic beads. Expression of PDGFR mRNA was examined by RT-PCR. After stimulating eosinophils with eotaxin, the phosphorylation of MAP kinases was examined by Western blotting with the antiphosphospecific MAP kinase antibody. The eotaxin-induced eosinophil chemotaxis was studied using Boyden chambers. Eosinophils expressed PDGFRbeta mRNA in 4 out of 8 donors, while PDGFRalpha mRNA was expressed in only 1 donor. Protein expression of PDGFR was also detectable in eosinophils from some donors. AG1295, a specific inhibitor of PDGFR, showed dose-dependent inhibition of eotaxin-induced MAP kinase phosphorylation in the eosinophils expressing PDGFRbeta mRNA. The chemotaxis of these eosinophils was significantly inhibited by AG1295 (n = 3). Our results suggest that PDGFR modifies the CCR3-MAP kinase signaling pathway and chemotactic response in some donors. The pharmacological targeting of PDGFR may be a new strategy to treat eosinophilic disorders.
  International Archives of Allergy and Immunology 02/2006; 140 Suppl 1:28-34. · 2.40 Impact Factor
• Article: [Reye syndrome and drug induced encephalopathy].

  Toshiaki Abe, Mayuko Sakae, Satoko Hanaka, Akiyo Matsumoto
  [show abstract] [hide abstract]
  ABSTRACT: Reye syndrome, characterized by acute encephalopathy, selective liver damages, a fatty degeneration in visceral organs and miserable prognosis, is probably caused by various drugs, especially antipyretic such as acetylsalicylate. The incidence of the disease has been decreased by prohibition of administration of aspirin for children with high fever, especially caused by influenza infection in western countries, also in Japan. The pathophysiology of the disease has extensively studied, however, still being unknown to be dissolved. Our previous study of lipid analysis of brain from experimental measles encephalitis revealed an increase of cholesterol ester and decrease of sphingomyelin. As cholesterol ester is synthesized from cholesterol and fatty acids catalyzed by acylCoA-acyltransferase(ACAT), ACAT activity can be increased in the experimental animal brain. In the present report, ACAT m-RNA could not be expressed in control brain but in the experimental animal brain, so ACAT may play a role in pathogenesis of Reye syndrome.
  Rinsho shinkeigaku = Clinical neurology 12/2003; 43(11):873-6.
• Article: Analysis of the comprehensive effects of polyunsaturated fatty acid on mRNA expression using a gene chip.

  Yoko Fujiwara, Masayo Yokoyama, Rumi Sawada, Yousuke Seyama, Masami Ishii, Shunichi Tsutsumi, Hiroyuki Aburatani, Satoko Hanaka, Hiroshige Itakura, Akiyo Matsumoto
  [show abstract] [hide abstract]
  ABSTRACT: To investigate the comprehensive effects of polyunsaturated fatty acids (PUFA) on gene expression, we analyzed changes of mRNA expression in PUFA-treated HepG2 cells using a DNA micro array. We incubated HepG2 cells for 24 h with or without 0.25 mM oleic acid (OA), arachidonic acid (AA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), and then compared the expression profiles of thousands of genes using a GeneChip. PUFA influenced the expression of various genes related to cell proliferation, growth and adhesion, as well as for many transcription factors including sterol regulatory element binding proteins (SREBP). Treatments with AA, EPA, and DHA repressed the expression of genes related to cholesterol and lipid metabolism. Moreover, data from gene chip analysis proved that PUPA reduced the expression ofprostasin, which is a serine protease. By measuring the mRNA levels of SREBPs, mevalonate pyrophosphatase and prostasin using quantitative RT-PCR, we confirmed the effect of PUFA revealed by gene chip analysis. These data might provide useful clues with which to explore novel functions of PUPA.
  Journal of Nutritional Science and Vitaminology 05/2003; 49(2):125-32. · 1.20 Impact Factor
• Article: Influence of polyunsaturated fatty acid on gene expression in HepG2 cells.

  Yoko Fujiwara, Masayo Yokoyama, Rumi Umeda-Sawada, Yousuke Seyama, Masami Ishii, Shunichi Tsutsumi, Hiroyuki Aburatani, Satoko Hanaka, Hiroshige Itakura, Akiyo Matsumoto
  Journal of atherosclerosis and thrombosis 02/2002; 9(3):157-62. · 2.69 Impact Factor
• Article: Gene expression related to cholesterol metabolism in mouse brain during development

  Satoko Hanaka, Toshiaki Abe, Hiroshige Itakura, Akiyo Matsumoto
  [show abstract] [hide abstract]
  ABSTRACT: Although a large amount of cholesterol is known to be needed for brain maturation and differentiation, cholesterol metabolism during these periods remains unclear. To elucidate the developmental regulation of cholesterol metabolism in the brain, we investigated the expression of 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34), low-density-lipoprotein (LDL) receptor and very-low-density-lipoprotein (VLDL)/apolipoprotein E (apo E) receptor (VLDL receptor) using RNase protection assay (RPA) to quantitate mRNA levels in mouse brain, liver and kidney during development. Messenger RNA levels of HMG-CoA reductase in the brain decreased with age, and those levels at −5 (5 days before birth) and 5 days after birth were significantly higher than the control level of adult mice. The period from −5 to 5 days might correspond to stages of active biogenesis of the membranes of brain cells. The mRNA level of HMG-CoA reductase in the liver was also high at −5 days; a finding that correlated with cell proliferation. On the other hand, mRNA levels of the LDL and VLDL receptors in the brain did not change markedly during development. These results suggest that de novo cholesterol biosynthesis in brain cells plays a major role in the supply of cholesterol to the developing brain, rather than the uptake of cholesterol from serum lipoproteins through lipoprotein receptors.
  Brain and Development.