論文 - 詳細
| RRC ID | 61512 |
|---|---|
| 著者 | Gemelli C, Dongmo BM, Ferrarini F, Grande A, Corsi L. |
| タイトル | Cytotoxic effect of hemin in colonic epithelial cell line: involvement of 18 kDa translocator protein (TSPO). |
| ジャーナル | Life Sci |
| Abstract |
AIMS:The aim of this study is to investigate the effect of hemin in colonic epithelial cells (Caco-2) cell proliferation and if this effect was due to a direct modulation of 18-kDa translocator protein (TSPO) and/or heme oxygenase type 1 (HO-1). MAIN METHODS:The main methods are as follow: cell proliferation and cell cytotoxic assays on Caco-2 cell lines treated with hemin in the presence or not of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11195) and Sn-protoporphyrin IX (Sn-PPIX), and immunoblotting for TSPO and HO-1 protein analysis, siRNA directed against TSPO. KEY FINDINGS:Hemin was shown to be toxic for the Caco-2 cell line in a concentration and time dependent manner. Although hemin was able to induce HO-1 in a dose dependent manner, a specific HO-1 inhibitor, Sn-PPIX, was unable to interfere with the effect of hemin on Caco-2 cells. Instead, PK 11195, a specific TSPO ligand, was able to counteract the effect of hemin, suggesting an important role of TSPO in the hemin activity. Cell viability assay further confirms the high cytotoxic effects exerted by hemin on Caco-2 cells expressing TSPO compared to the siRNA-TSPO targeted cells. In addition, hemin was able to decrease significantly the TSPO protein density in a dose dependent manner after 24h of incubation. SIGNIFICANCE:The interaction and the consecutive down regulation of TSPO by hemin played an important role in the control of Caco-2 cell viability. The presented data suggest that TSPO might contribute to protect cells from potential toxic compounds such as free tetrapyrroles, candidating this receptor as a survival receptor protein. |
| 巻・号 | 107(1-2) |
| ページ | 14-20 |
| 公開日 | 2014-6-27 |
| DOI | 10.1016/j.lfs.2014.04.026 |
| PII | S0024-3205(14)00446-9 |
| PMID | 24792517 |
| MeSH | Antineoplastic Agents / pharmacology Apoptosis / drug effects* Blotting, Western Caco-2 Cells / drug effects Caco-2 Cells / metabolism Cell Proliferation / drug effects* Enzyme Inhibitors / pharmacology Gene Expression Regulation, Neoplastic / drug effects* Heme Oxygenase-1 / antagonists & inhibitors Heme Oxygenase-1 / metabolism Hemin / pharmacology* Humans Isoquinolines / pharmacology Metalloporphyrins / pharmacology Protoporphyrins / pharmacology RNA, Small Interfering / genetics Receptors, GABA / chemistry Receptors, GABA / genetics Receptors, GABA / metabolism* |
| IF | 3.647 |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) |