RRC ID 42818
著者 Nagashima H, Maeda-Nakamura K, Iwashita K, Goto T.
タイトル Induced secretion of insulin-like growth factor binding protein-1 (IGFBP-1) in human hepatoma cell HepG2 by rubratoxin B.
ジャーナル Arch Toxicol
Abstract The induction of insulin-like growth factor binding protein-1 (IGFBP-1) secretion by rubratoxin B was investigated using human hepatoma cell line HepG2; we also documented the involvement of stress-activated MAP kinases [c-Jun-N-terminal kinases (JNKs) and p38s] in this process. Rubratoxin B dramatically enhanced IGFBP-1 secretion, which peaked at a concentration of 40 microg/ml. The amount of IGFBP-1 mRNA increased with time and plateaued at 6 h. Compared with the amounts of IGFBP-1 secreted, the induction ratios of transcription were much smaller, indicating that IGFBP-1 secretion is regulated chiefly post-transcriptionally. The result of concomitant treatment with rubratoxin B and JNK inhibitor indicated that JNKs do not affect rubratoxin B-induced IGFBP-1 secretion. Alternatively, rubratoxin B-associated induction of IGFBP-1 secretion was marked in the absence of p38 inhibitor but attenuated in its presence. Therefore, p38s appear to stimulate rubratoxin B-induced IGFBP-1 secretion. Treatment with p38 inhibitor slightly increased the amount of rubratoxin B-induced IGFBP-1 mRNA. However this induction ratio was smaller than that of rubratoxin B-induced secretion, suggesting that p38s regulate IGFBP-1 secretion both transcriptionally and post-transcriptionally. In this study, we showed that rubratoxin B induces IGFBP-1 levels in HepG2 cells and p38s contribute to this process.
巻・号 81(5)
ページ 347-51
公開日 2007-5-1
DOI 10.1007/s00204-006-0162-5
PMID 17109117
MeSH Anthracenes / pharmacology Anti-Inflammatory Agents, Non-Steroidal / pharmacology Cell Line, Tumor Dose-Response Relationship, Drug Drug Synergism Enzyme Inhibitors / pharmacology Humans Imidazoles / pharmacology Insulin-Like Growth Factor Binding Protein 1 / genetics* Insulin-Like Growth Factor Binding Protein 1 / metabolism* JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors JNK Mitogen-Activated Protein Kinases / metabolism Mycotoxins / pharmacology* Pyridines / pharmacology RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Time Factors p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors p38 Mitogen-Activated Protein Kinases / metabolism
IF 5.059
引用数 8
WOS 分野 TOXICOLOGY
リソース情報
ヒト・動物細胞 Hep G2