Toxicological evaluation of z24, a novel indolin-2-ketone compound, in cultured human liver cells using toxicogenomic techniques
文献类型：期刊论文
| 作者 | Wang, Quanjun1; Zhao, Jianyu2; Yang, Baohua1; Jiang, Ying3; Wu, Chunqi1; Zheng, Zhibing1; Yu, Shouzhong1; Yuan, Benli1; Li, Song1; Liao, Mingyang1 |
| 刊名 | International journal of toxicology
 |
| 出版日期 | 2010-07-01 |
| 卷号 | 29期号:4页码:380-390 |
| 关键词 | Mechanism Toxicogenomics Z24 |
| ISSN号 | 1091-5818 |
| DOI | 10.1177/1091581810370373 |
| 通讯作者 | Liao, mingyang(liaomingy@yahoo.com.cn) |
| 英文摘要 | The current study was designed to investigate the toxicity of 3z-3-[((1)h-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1, 3-2h-indol-2-one (z24), a novel synthetic indolin-2-ketone small molecule compound, using toxicogenomic techniques (complementary dna [cdna] microarray). bioinformatic analysis suggested that the main functions of genes with altered expression were consistent with liver cell regeneration, apoptosis, metabolism of energy and fat, and the death receptor (dr)-mediated apoptosis-signaling pathway. death receptor 4, bcl-2, bcl-xl, caspase 3, and cytochrome c, which are involved in the dr-mediated apoptosis-signaling pathway, were altered after z24 treatment as determined by western blotting analysis. when hepatocarcinoma cell line (hepg2 cells) treated with z24 at 0.248 mmol/l for 24 hours, dna fragmentation reached a maximum, and examination of cell morphology showed typical signs of apoptosis. these results indicate that z24 can initiate apoptosis in hepatocytes, which in turn causes hepatotoxicity. a possible toxicological mechanism is that apoptosis was induced in hepatocytes by initiating the dr-mediated signal transduction pathway. apoptosis of hepatocytes might lead to impairment of energy and lipid metabolism and provoke hepatocyte necrosis or inflammation, resulting in hepatotoxicity. |
| WOS关键词 | DNA FRAGMENTATION ; IN-VITRO ; INDUCED HEPATOTOXICITY ; EXPRESSION PATTERNS ; SIGNALING PATHWAYS ; APOPTOSIS ; GENE ; RECEPTOR ; DEATH ; MITOCHONDRIA |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| WOS类目 | Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000280884500004 |
| 出版者 | SAGE PUBLICATIONS INC |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2408961 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Liao, Mingyang |
| 作者单位 | 1.Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China 2.Chinese Acad Sci, Coll Life Sci, Grad Univ, Beijing, Peoples R China 3.Beijing Proteome Res Ctr, Beijing Inst Radiat Med, Dept Genom & Prote, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Quanjun,Zhao, Jianyu,Yang, Baohua,et al. Toxicological evaluation of z24, a novel indolin-2-ketone compound, in cultured human liver cells using toxicogenomic techniques[J]. International journal of toxicology,2010,29(4):380-390. |
| APA | Wang, Quanjun.,Zhao, Jianyu.,Yang, Baohua.,Jiang, Ying.,Wu, Chunqi.,...&Liao, Mingyang.(2010).Toxicological evaluation of z24, a novel indolin-2-ketone compound, in cultured human liver cells using toxicogenomic techniques.International journal of toxicology,29(4),380-390. |
| MLA | Wang, Quanjun,et al."Toxicological evaluation of z24, a novel indolin-2-ketone compound, in cultured human liver cells using toxicogenomic techniques".International journal of toxicology 29.4(2010):380-390. |
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来源：中国科学院大学
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