Abstract
Suspension of human epidermal cells in methylcellulose-containing medium induces CYP1A1 by a mechanism requiring functional Ah receptor (AhR). In present work CYP1A1 mRNA was induced in a variety of cultured rat epithelial cells by suspension, but the induction was transient, with CYP1A1 mRNA reaching maximal levels by 5 h and disappearing by 12 h. Though the methylcellulose itself contained no detectable ligand, (a) suspension activated the AhR, as judged by mobility shift assays, (b) the AhR competitive inhibitor α-naphthoflavone inhibited suspension-mediated induction, and (c) induction was dependent upon dioxin responsive transcriptional elements in the CYP1A1 promoter. The rapid disappearance of CYP1A1 mRNA after 5 h of suspension was unaffected by the addition of TCDD but was prevented by the inclusion of the protein synthesis inhibitor cycloheximide. Thus the downregulation appears to be mediated by a novel short-lived protein induced or activated by suspension.
Original language | English (US) |
---|---|
Pages (from-to) | 154-162 |
Number of pages | 9 |
Journal | Archives of Biochemistry and Biophysics |
Volume | 393 |
Issue number | 1 |
DOIs | |
State | Published - Sep 1 2001 |
Keywords
- Ah receptor
- CYP1A1
- Keratinocytes
- Methylcellulose
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology