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学科主题: Pharmacology & Pharmacy; Toxicology
题名: Effects of fluorotelomer alcohol 8/2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade
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
通讯作者: Zhang, XW, Nanjing Univ, Sch Environm, Nanjing 210089, Peoples R China
关键词: Steroid hormone production ; Gene expression ; Adenylate cyclase ; FTOH
刊名: TOXICOLOGY AND APPLIED PHARMACOLOGY
发表日期: 2010-09-15
DOI: 10.1016/j.taap.2010.06.016
卷: 247, 期:3, 页:222-228
收录类别: SCI
文章类型: Article
部门归属: [Zhang, Xiaowei; Giesy, John P.] Nanjing Univ, Sch Environm, Nanjing 210089, Peoples R China; [Zhang, Xiaowei; Giesy, John P.] Nanjing Univ, State Key Lab Pollut Control & Resource Reuse, Nanjing 210089, Peoples R China; [Liu, Chunsheng; Zhou, Bingsheng] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China; [Liu, Chunsheng] Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China; [Chang, Hong; Jones, Paul; Wiseman, Steve; Naile, Jonathan; Hecker, Markus; Giesy, John P.] Univ Saskatchewan, Biomed Sci & Toxicol Ctr, Dept Vet, Saskatoon, SK, Canada; [Hecker, Markus] ENTRIX Inc, Saskatoon, SK, Canada; [Giesy, John P.] City Univ Hong Kong, Dept Biol & Chem, Kowloon, Hong Kong, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: National Natural Science Foundation of China [20890113, 20877094]; NSERC of Canada [326415-07]; WED Canada [6578, 6807]
类目[WOS]: Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]: Pharmacology & Pharmacy ; Toxicology
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.
关键词[WOS]: ADRENOCORTICAL CARCINOMA-CELLS ; AROMATASE CYP19 ACTIVITY ; MALE-RATS ; IN-VITRO ; PERFLUORODODECANOIC ACID ; PERFLUOROALKYL ACIDS ; GENE-EXPRESSION ; MECHANISMS ; CHEMICALS ; LINE
语种: 英语
WOS记录号: WOS:000281658300007
ISSN号: 0041-008X
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/13685
Appears in Collections:水环境工程研究中心_期刊论文

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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

Recommended Citation:
Liu, Chunsheng; Zhang, Xiaowei; Chang, Hong; Jones, Paul; Wiseman, Steve; Naile, Jonathan; Hecker, Markus; Giesy, John P.; Zhou, Bingsheng.Effects of fluorotelomer alcohol 8/2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade,TOXICOLOGY AND APPLIED PHARMACOLOGY,2010,247(3):222-228
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