Abstract
The objective of this study is to determine the mechanism underlying ethanol‐induced expression of solute carrier family 7 member 11 (Slc7a11). Quantitative real‐time RT‐PCR assay, western blot analysis, promoter activity assays and chromatin immunoprecipitation analysis were performed in this study. Our data demonstrated that ethanol significantly increased Slc7a11 mRNA and protein expression in mouse hepatic stellate cells. Deletion of 20‐bp DNA sequence between −2044 to −2024 upstream of the transcription start site significantly increased the basal activity, and completely abolished the ethanol‐induced activity of the Slc7a11 promoter. DNA sequence analysis reveals a biding motif for octamer‐binding transcription factor 1 (OCT‐1) in this deleted fragment. Similarly, mutation of this OCT‐1 binding motif significantly increased the basal promoter activity and abolished the response to ethanol. In addition, Ethanol exposure significantly inhibited OCT‐1 binding to the Slc7a11 promoter region, while the OCT‐1 mRNA and protein levels were comparable in cells treated with or without ethanol. Results from the present study suggest that OCT‐1 functions as a repressor on the Slc7a11 promoter, and that ethanol inhibits OCT‐1 binding to the Slc7a11 promoter, and therefore increases Slc7a11 expression. Grant support: R01HL089382 (ZhongMao Guo) and SC1HL101431 (Hong Yang).
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
