Novel potential of tunicamycin as an activator of the aryl hydrocarbon receptor -- dioxin responsive element signaling pathway.
Tunicamycin is a well-known inhibitor of protein glycosylation and used as an inducer of endoplasmic reticulum (ER) stress. We found that tunicamycin induced expression of cytochrome P450 1A1 in a dose-dependent manner. Like dioxin, the transcriptional induction was associated with dose-dependent activation of the dioxin responsive element (DRE). This effect was independent of inhibition of protein glycosylation or induction of ER stress. Pharmacological and genetic inhibition of the aryl hydrocarbon receptor (AhR) significantly attenuated activation of DRE by tunicamycin. These results elucidated the novel potential of tunicamycin as an activator of the AhR -- DRE signaling pathway.
Horikawa
Kyohei
K
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.
Oishi
Naoki
N
Nakagawa
Jin
J
Kasai
Ayumi
A
Hayakawa
Kunihiro
K
Hiramatsu
Nobuhiko
N
Takano
Yosuke
Y
Yokouchi
Makiko
M
Yao
Jian
J
Kitamura
Masanori
M
D000818:Animals; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004147:Dioxins / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006031:Glycosylation; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects*; D014415:Tunicamycin / Q000494:pharmacology*
D004147:Dioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014415:Tunicamycin; D019363:Cytochrome P-450 CYP1A1