title: 2,2,2-Trichloroethanol lengthens the circadian period of Bmal1-driven circadian bioluminescence rhythms in U2OS cells.
abstract: 2,2,2-Trichloroethanol (TCOH) is responsible for the pharmacological actions of chloral hydrate (CH), and is a major metabolite of trichloroethylene. Human exposure to TCOH is known to be increasing. Recently, it was reported that TCOH causes a significant phase delay of Per2 expression in mouse liver when injected daily over the course of several days. However, it is not clear whether TCOH directly modulates the molecular clock. In the present study we used a cell-based assay system to test this possibility. We found that the daily oscillation period of Bmal1 was lengthened to 3 h following treatment with 1.5 mM TCOH, and increased to 5 h with 3 mM TCOH treatment. However, low concentrations of TCOH had no noticeable effects. The effect of TCOH on Per2 oscillation was marginal. Interestingly, serum from rats anesthetized with CH also modulated Bmal1 period, suggesting that exposure to anesthesia should be taken into consideration for circadian rhythm studies. In summary, our study reveals a direct regulation of TCOH on molecular clock.
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Parkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing 100053, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Parkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing 100053, PR China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Parkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing 100053, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Parkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing 100053, PR China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Parkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing 100053, PR China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Parkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing 100053, PR China. Electronic address: Yanningcai@yahoo.com.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Cai
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics*; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics; D002460:Cell Line; D002697:Chloral Hydrate / Q000494:pharmacology / Q000633:toxicity; D002940:Circadian Rhythm / Q000187:drug effects* / Q000235:genetics*; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000633:toxicity; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics; D056950:Period Circadian Proteins / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D006993:Hypnotics and Sedatives; C064353:NR1D1 protein, human; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; C421902:PER2 protein, human; D056950:Period Circadian Proteins; D002697:Chloral Hydrate; D005023:Ethylene Chlorohydrin; C005849:2,2,2-trichloroethanol; D056926:CLOCK Proteins
keywords: 2,2,2-Trichloroethanol; Bioluminescence; Bmal1; Cell culture; Per2; Reporter