論文 - 詳細
| RRC ID | 18648 |
|---|---|
| 著者 | Ishizuka T, Watanabe Y. |
| タイトル | α₁-Adrenoceptor stimulation enhances leukemia inhibitory factor-induced proliferation of mouse-induced pluripotent stem cells. |
| ジャーナル | Eur J Pharmacol |
| Abstract |
Since the clinical use of induced pluripotent stem (iPS) cells may overcome the current obstacles in stem cell-based therapy, the molecular mechanisms that regulate iPS cell proliferation are of great interest. Therefore, in the present study, we determined the involvement of α(1)-adrenoceptor in the proliferation of mouse iPS cells. The selective α(1)-adrenoceptor agonist l-phenylephrine dose-dependently increased the proliferation of mouse iPS cells cultured in a medium with leukemia inhibitory factor (LIF). Pretreatment with either selective α(1)-adrenoceptor antagonists or protein kinase C (PKC) inhibitors significantly inhibited l-phenylephrine-induced DNA synthesis. The treatment with an IP(3) receptor agonist significantly enhanced LIF-induced DNA synthesis. On the other hand, we confirmed that the intracellular calcium level was increased by the treatment with l-phenylephrine. Thus, intracellular calcium release or PKC activation induced by α(1)-adrenoceptor activation may lead to the enhancement of DNA synthesis. In addition, pretreatment with mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor PD98059 or phosphatidylinositol-3 phosphate kinase (PI3K) inhibitor LY294002 significantly inhibited l-phenylephrine-induced DNA synthesis. Treatment with l-phenylephrine significantly increased Akt or p44/42 MAPK phosphorylation. α(1)-Adrenoceptor expression in mouse iPS cells was confirmed by immunofluorescence staining and western blotting analysis. In mouse iPS cells cultured with LIF, stimulation with l-phenylephrine significantly increased the proportion of cells in the S and G(2)/M phases and decreased that in the G(1) phase. These results suggest that stimulation with α(1)-adrenoceptor may enhance DNA synthesis and proliferation of mouse iPS cells cultured with LIF via augmentation of both the MEK/MAPK and the PI3K/Akt pathways. |
| 巻・号 | 668(1-2) |
| ページ | 42-56 |
| 公開日 | 2011-10-1 |
| DOI | 10.1016/j.ejphar.2011.06.026 |
| PII | S0014-2999(11)00733-3 |
| PMID | 21745467 |
| MeSH | Adrenergic alpha-1 Receptor Agonists / pharmacology Adrenergic alpha-1 Receptor Antagonists / pharmacology Animals Cell Culture Techniques Cell Cycle / drug effects Cell Line Cell Proliferation / drug effects DNA / biosynthesis Enzyme Activation / drug effects Gene Expression Regulation / drug effects Humans Intracellular Space / drug effects Intracellular Space / metabolism Leukemia Inhibitory Factor / pharmacology* Mice Mitogen-Activated Protein Kinases / metabolism Phenylephrine / pharmacology Phosphatidylinositol 3-Kinases / metabolism Pluripotent Stem Cells / cytology* Pluripotent Stem Cells / drug effects* Pluripotent Stem Cells / metabolism Prazosin / pharmacology Protein Kinase C / metabolism Proto-Oncogene Proteins c-akt / metabolism Proto-Oncogene Proteins c-myc / metabolism Receptors, Adrenergic, alpha-1 / metabolism* STAT Transcription Factors / metabolism Tumor Suppressor Protein p53 / metabolism |
| IF | 3.263 |
| 引用数 | 7 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | iPS-MEF-Ng-20D-17(APS0001) |