Chemical control of cell differentiation and its commitment of blood cells

细胞分化的化学控制及其对血细胞的承诺

• 批准号: 11672209
• 负责人: KOISO Yukiko
• 金额: $ 2.18万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672209/
• 关键词: 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

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.

人髓性白血病K562细胞被双向诱导分化为成熟细胞，即，氯化血红素诱导红细胞分化，而12-O-十四烷酰基佛波醇13-乙酸酯（TPA）诱导分化为单核细胞。TPA是血红素加氧酶（HO）的强诱导剂，HO将血红素分解代谢为胆绿素。HO抑制剂锡原卟啉（SnPP）可抑制TPA诱导的K562细胞向单核细胞分化。我们发现TPA抑制氯化血红素诱导的K562细胞向红系分化，而维甲酸则增强其向红系分化的能力，HO抑制剂锡原卟啉（SnPP）抑制TPA诱导的K562细胞向单核细胞分化。研究还发现，SnPP和TPA联合处理K562细胞可诱导K562细胞向红系分化，但单独使用SnPP或单独使用TPA不会诱导红系分化，这表明HO在分化方向转换中发挥作用。

项目成果

T.Ishioka: "Novel non steroidal/non amilide type androgen antagonists with an isoxazolone moidty"Bioorg. Med. Chem. 10. 1555-1566 (2002)

T.Ishioka：“具有异恶唑酮模式的新型非类固醇/非酰胺型雄激素拮抗剂”Bioorg。

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)

Motonori Tsuji、ΔYukiko Koiso、Δ Hiroyasu Takahashi、Δ Yuichi Hashimoto、Δ 和 Yasuyuki Endo：“以二碳-氯-十二硼烷作为疏水性药效基团的肿瘤坏死因子产生调节剂”Biol.，Pharm.，Bull. 513。 -516 (2000)

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)

H.Kakuta：“新型特异性嘌呤霉素敏感氨肽酶抑制剂：3-(2,6-二乙基苯基)-2,4(1H,3H)喹唑啉二酮和N-(2,6-二乙基苯基)-2-氨基-4H

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

H. Kakuta，Δ Y，Koiso，Δ H. Takahashi，Δ K.Nagasawa，Δ Y. Hashimoto：“新型特异性嘌呤霉素敏感氨肽酶抑制剂：3-(2,6-二乙基苯基)-2,4(1H,3H) )-喹唑啉二酮和 N-(2,6-二乙基苯基)-2-氨基-4H-3,1-苯并恶嗪-4-酮。”杂环。55-8

T.Ishioka: "Novel non-steroidal/non-anilide type androgen antagonists with an isoxzolone moiety"Bioorg. Med. Chem.. 10・5. 1555-1566 (2002)

T.Ishioka：“具有异恶唑酮部分的新型非甾体/非苯胺型雄激素拮抗剂”Bioorg.Med.10・5（2002）。