Effects of fluorotelomer alcohol 8/2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade
文献类型：期刊论文
| 作者 | Liu, Chunsheng3,4; Zhang, Xiaowei1,2; Chang, Hong5; Jones, Paul5; Wiseman, Steve5; Naile, Jonathan5; Hecker, Markus5,6; Giesy, John P.1,2,5,7; Zhou, Bingsheng3 |
| 刊名 | TOXICOLOGY AND APPLIED PHARMACOLOGY
 |
| 出版日期 | 2010-09-15 |
| 卷号 | 247期号:3页码:222-228 |
| 关键词 | Steroid hormone production Gene expression Adenylate cyclase FTOH |
| ISSN号 | 0041-008X |
| 通讯作者 | Zhang, XW, Nanjing Univ, Sch Environm, Nanjing 210089, Peoples R China |
| 中文摘要 | Previous studies have demonstrated that perfluorinated chemicals (PFCs) can affect reproduction by disruption of steroidogenesis in experimental animals. However, the underlying mechanism(s) of this disruption remain unknown. Here we investigated the effects and mechanisms of action of 1H, 1H, 2H, 2H-perfluoro-decan-1-ol (8:2 FTOH) on steroidogenesis using a human adrenocortical carcinoma cell line (H295R) as a model. H295R cells were exposed to 0, 7.4, 22.2 or 66.6 mu M 8:2 FTOH for 24 h and productions of progesterone, 17 alpha-OH-progesterone, androstenedione, testosterone, deoxycorticosterone, corticosterone and cortisol were quantified by HPLC-MS/MS. With the exception of progesterone, 8:2 FTOH treatment significantly decreased production of all hormones in the high dose group. Exposure to 8:2 FTOH significantly down-regulated cAMP-dependent mRNA expression and protein abundance of several key steroidogenic enzymes, including StAR, CYP11A, CYP11B1, CYP11B2, CYP17 and CYP21. Furthermore, a dose-dependent decrease of cellular cAMP levels was observed in H295R cells exposed to 8:2 FTOH. The observed responses are consistent with reduced cellular CAMP levels. Exposure to 8:2 FTOH resulted in significantly less basal (+GTP) and isoproterenol-stimulated adenylate cyclase activities, but affected neither total cellular ATP level nor basal (-GTP) or NaF-stimulated adenylate cyclase activities, suggesting that inhibition of steroidogenesis may be due to an alteration in membrane properties. Metabolites of 8:2 FTOH were not detected by HPLC-MS/MS, suggesting that 8:2 FTOH was not metabolized by H295R cells. Overall, the results show that 8:2 FTOH may inhibit steroidogenesis by disrupting the cAMP signalling cascade. (C) 2010 Elsevier Inc. All rights reserved. |
| 英文摘要 | Previous studies have demonstrated that perfluorinated chemicals (PFCs) can affect reproduction by disruption of steroidogenesis in experimental animals. However, the underlying mechanism(s) of this disruption remain unknown. Here we investigated the effects and mechanisms of action of 1H, 1H, 2H, 2H-perfluoro-decan-1-ol (8:2 FTOH) on steroidogenesis using a human adrenocortical carcinoma cell line (H295R) as a model. H295R cells were exposed to 0, 7.4, 22.2 or 66.6 mu M 8:2 FTOH for 24 h and productions of progesterone, 17 alpha-OH-progesterone, androstenedione, testosterone, deoxycorticosterone, corticosterone and cortisol were quantified by HPLC-MS/MS. With the exception of progesterone, 8:2 FTOH treatment significantly decreased production of all hormones in the high dose group. Exposure to 8:2 FTOH significantly down-regulated cAMP-dependent mRNA expression and protein abundance of several key steroidogenic enzymes, including StAR, CYP11A, CYP11B1, CYP11B2, CYP17 and CYP21. Furthermore, a dose-dependent decrease of cellular cAMP levels was observed in H295R cells exposed to 8:2 FTOH. The observed responses are consistent with reduced cellular CAMP levels. Exposure to 8:2 FTOH resulted in significantly less basal (+GTP) and isoproterenol-stimulated adenylate cyclase activities, but affected neither total cellular ATP level nor basal (-GTP) or NaF-stimulated adenylate cyclase activities, suggesting that inhibition of steroidogenesis may be due to an alteration in membrane properties. Metabolites of 8:2 FTOH were not detected by HPLC-MS/MS, suggesting that 8:2 FTOH was not metabolized by H295R cells. Overall, the results show that 8:2 FTOH may inhibit steroidogenesis by disrupting the cAMP signalling cascade. (C) 2010 Elsevier Inc. All rights reserved. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 学科主题 | Pharmacology & Pharmacy; Toxicology |
| 类目[WOS] | Pharmacology & Pharmacy ; Toxicology |
| 研究领域[WOS] | Pharmacology & Pharmacy ; Toxicology |
| 关键词[WOS] | ADRENOCORTICAL CARCINOMA-CELLS ; AROMATASE CYP19 ACTIVITY ; MALE-RATS ; IN-VITRO ; PERFLUORODODECANOIC ACID ; PERFLUOROALKYL ACIDS ; GENE-EXPRESSION ; MECHANISMS ; CHEMICALS ; LINE |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China [20890113, 20877094]; NSERC of Canada [326415-07]; WED Canada [6578, 6807] |
| 语种 | 英语 |
| WOS记录号 | WOS:000281658300007 |
| 公开日期 | 2010-12-23 |
| 源URL | [http://ir.ihb.ac.cn/handle/342005/13685]  |
| 专题 | 水生生物研究所_水环境工程研究中心_期刊论文 |
| 作者单位 | 1.Nanjing Univ, Sch Environm, Nanjing 210089, Peoples R China 2.Nanjing Univ, State Key Lab Pollut Control & Resource Reuse, Nanjing 210089, Peoples R China 3.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China 4.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China 5.Univ Saskatchewan, Biomed Sci & Toxicol Ctr, Dept Vet, Saskatoon, SK, Canada 6.ENTRIX Inc, Saskatoon, SK, Canada 7.City Univ Hong Kong, Dept Biol & Chem, Kowloon, Hong Kong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Chunsheng,Zhang, Xiaowei,Chang, Hong,et al. Effects of fluorotelomer alcohol 8/2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2010,247(3):222-228. |
| APA | Liu, Chunsheng.,Zhang, Xiaowei.,Chang, Hong.,Jones, Paul.,Wiseman, Steve.,...&Zhou, Bingsheng.(2010).Effects of fluorotelomer alcohol 8/2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade.TOXICOLOGY AND APPLIED PHARMACOLOGY,247(3),222-228. |
| MLA | Liu, Chunsheng,et al."Effects of fluorotelomer alcohol 8/2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade".TOXICOLOGY AND APPLIED PHARMACOLOGY 247.3(2010):222-228. |
入库方式： OAI收割
来源：水生生物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。