Chemical control of cell differentiation and its commitment of blood cells

• Project/Area Number: 11672209
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 医薬分子機能学
• Research Institution: The University of Tokyo
• Principal Investigator: KOISO Yukiko Institute of Molecular and cellular biosciences, assistant professor, 分子細胞生物学研究所, 助手 (50092200)
• Project Period (FY): 1999 – 2001
• Project Status: Completed (Fiscal Year 2001)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
• Keywords: K562 cells / heme oxygenase / cell differentiation / TPA / PDI / フォルボールエステル / プロテインジスルフィドイソメラーゼ / 分化誘導剤 / フォルボールエステル(TPA) / PKC / PDI / 細胞分化

Research Abstract

Human myeloid leukemia K562 cells be induced to differentiate to mature cells bidirectionary, i.e., hemin induces erythroid differentiation, while 12-O-tetradecanoylphorbol 13-acetate (TPA) induces differentiation to monocytes. TPA is a potent inducer of heme oxygenase (HO), which catabolizes heme to biliverdin. An HO inhibitor, tin protoporphyrin (SnPP), suppresses TPA-induced K562 cell differentiation to monocytes. We show that TPA suppresses hemin-induced erythroid differentiation of K562 cells, while retinoids augment it. Futher, an HO inhibitor, tin protoporphyrin (SnPP), suppresses TPA-induced K562 cell differentiation to monocytes. It was also found that co-treatment of K562 cells with SnPP and TPA induces erythroid differentiation of K562 cells, though SnPP alone or TPA alone does not induce erythroid differentiation, suggesting a role of HO in the directional switch of differentiation.

Research Products

• [Publications] H.Kakuta: "Novel specific puromycin-sensitive aminopeptidase inhibitors : 3-(2,6-diethylphenyl)-2,4(1H,3H) quinazoline-dione and N-(2,6-Diethylphenyl)-2-amino-4H-3,1-benzoxazin-4-one"Heterocycles. 55. 1433-1438 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Ishioka: "Novel non steroidal/non amilide type androgen antagonists with an isoxazolone moidty"Bioorg. Med. Chem. 10. 1555-1566 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yukiko Koiso, Δ Yasuyuki Fujimoto,Δ Daisuke Matsumura,Δ Osamu Nakajima,Δ and Yuichi Hashimoto: "Modification by heme oxygenase inhibitor, tin protoporphyrin, of cellular differentiation of human myeloid leukemia K562 cell line"Biol. Pharm. Bull. 22-4. 439-440 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yukiko Koiso,Δ Yasuyuki Fujimoto, Δ Daisuke Matsumura,Δ Osamu Nakajima,Δ and Yuichi Hashimoto: "Chemical control of cell differentiation of human myeloleukemia K562 cell line"YAKUGAKU ZASSHI. 120-1. 104-112 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Motonori Tsuji,ΔYukiko Koiso,Δ Hiroyasu Takahashi,Δ Yuichi Hashimoto,Δ and Yasuyuki Endo: "Modulators of tumor necrosis factor aproduction bearing dicarba-closo-dodecaborane as a hydrophobic pharmacophore"Biol., Pharm., Bull. 24-4. 513-516 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] H. Kakuta,Δ Y,Koiso,Δ H. Takahashi,Δ K.Nagasawa,Δ Y. Hashimoto: "Novel specific puromycin-sensitive aminopeptidase inhibitors : 3-(2,6-diethylphenyl)-2,4(1H,3H)-quinazolinedione and N-(2,6-diethylphenyl)-2-amino-4H-3,1-benzoxazin-4-one."Heterocycles. 55-8. 1433-1438 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Toshiyasu Ishioka,Δ Asako Kubo,Δ Yukiko Koiso,Δ Kazuo Nagasawa,Δ Akiko Itai,Δ and Yuichi Hashimoto: "Novel non-steroidal/non-anilide type androgen antagonists with an isoxazolone moiety"Bioorg. Med. Chem.. 10-5. 1555-1566 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] H.Kakuta: "Novel specific puromycin-sensitive aminopeptidase inhibitors : 3-(2, 6-diethylphenyl)-2, 4(1H, 3H)-quinazolonedione and N-(2, 6-diethylphenyl)-2-amino-4H-3, 1-benzoxazin-4-one"Heterocycles. 55・8. 1433-1438 (2001)
• [Publications] T.Ishioka: "Novel non-steroidal/non-anilide type androgen antagonists with an isoxzolone moiety"Bioorg. Med. Chem.. 10・5. 1555-1566 (2002)
• [Publications] 小磯邦子: "ヒト白血病細胞K562細胞の細胞分化における化学制御"薬学雑誌. 120. 104-112 (2000)
• [Publications] M.Tsuji: "Modulators of tumor necrosis factor α production bearing dicarba- closo- dodecaborane as a hydrophobic pharmacophore"Biol.Pharm.Bull.. 24. 513-516 (2000)
• [Publications] H.Takahashi: "Anti-androgenic activity of substituted azo- and azoxy-benzene derivatives"Biol.Pharm.Bull. 23. 1387-1390 (2000)
• [Publications] Yukiko Koiso: "Modification by Heme oxygenase Inhibitor, Tin Protoporphyrin, of Cellular Differentiation of Human Myeloid Leukemia K562 CellLine"Biol. Pharm. Bull. 22(4). 439-440 (1999)