Piperonyl butoxide activates c-Jun and ATF-2 in the hepatocytes of mice.
In order to clarify the possible mechanism of hepatocarcinogenesis induced by piperonyl butoxide, we attempted to identify the transcription factor activated by piperonyl butoxide in the male ICR mouse liver. Administration of 0.6% piperonyl butoxide for 24 h elevated the level of liver nuclear proteins that bind to an AP-1 consensus oligonucleotide, and these proteins demonstrated a supershift with the anti-c-Jun antibody. Additionally, immunoblot analysis revealed that piperonyl butoxide induced c-Jun phosphorylation within 8 h of administration, and phosphorylated ATF-2 was detected after 24 h of piperonyl butoxide treatment. Immunohistochemical analysis also demonstrated the presence of phosphorylated ATF-2 in the hepatocyte nuclei of mice fed with 0.6% piperonyl butoxide for 24 h. Furthermore, piperonyl butoxide induced ATF-2 phosphorylation in TLR-3, a mouse immortalized hepatocyte cell line. These results indicated that piperonyl butoxide activated c-Jun and ATF-2 in mouse hepatocytes during the early stage of hepatocarcinogenesis.
Muguruma
Masako
M
Laboratory of Veterinary Pathology, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai, Fuchu, Tokyo 183-8509, Japan. lauramh@pd6.so-net.ne.jp
Arai
Katsuhiko
K
Moto
Mitsuyoshi
M
Nishimura
Jihei
J
Dewa
Yasuaki
Y
Mitsumori
Kunitoshi
K
D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation; D010882:Piperonyl Butoxide / Q000633:toxicity*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism
D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D002273:Carcinogens; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D010882:Piperonyl Butoxide