| RRC ID |
42580
|
| 著者 |
Nagashima H, Maeda-Nakamura K, Iwashita K, Goto T.
|
| タイトル |
Induced secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) in vivo and in vitro by hepatotoxin rubratoxin B.
|
| ジャーナル |
Food Chem Toxicol
|
| Abstract |
To elucidate the mechanism of rubratoxin B toxicity, we investigated rubratoxin B-induced secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) in mice and cultured cells; we also documented the involvement of stress-activated MAP kinases (c-Jun-N-terminal kinases [JNKs] and p38s) in this process. Rubratoxin B significantly (P<0.05) induced serum TIMP-1 levels in mice. Because TIMP-1 is thought to play a crucial role in the process of liver fibrosis, rubratoxin B may cause liver fibrosis. Rubratoxin B enhanced TIMP-1 secretion in HepG2 cells to a peak level of approximately 40 microg/ml. The amount of TIMP-1 mRNA increased with the duration of rubratoxin B treatment; and this hepatotoxin appears to induce TIMP-1 secretion through a transcriptional control mechanism. Unlike similar treatment with rubratoxin B and JNK inhibitor, concomitant treatment with rubratoxin B and p38 inhibitor increased rubratoxin B-induced TIMP-1 secretion, suggesting that p38s (but not JNKs) antagonize this process. In addition, treatment with p38 inhibitor slightly increased the amount of rubratoxin B-induced TIMP-1 mRNA, suggesting that p38s control rubratoxin B-induced TIMP-1 secretion chiefly post-transcriptionally. In this study, we showed that rubratoxin B induces TIMP-1 production in vivo and in vitro and that p38s antagonize rubratoxin B-induced TIMP-1 secretion.
|
| 巻・号 |
44(7)
|
| ページ |
1138-43
|
| 公開日 |
2006-7-1
|
| DOI |
10.1016/j.fct.2006.01.012
|
| PII |
S0278-6915(06)00018-4
|
| PMID |
16530906
|
| MeSH |
Actins / biosynthesis
Animals
Cell Line
Enzyme Inhibitors / pharmacology
MAP Kinase Kinase 4 / antagonists & inhibitors
Male
Mice
Mice, Inbred C3H
Mitogen-Activated Protein Kinases / metabolism
Mycotoxins / pharmacology*
RNA, Messenger / biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Stimulation, Chemical
Tissue Inhibitor of Metalloproteinase-1 / blood
Tissue Inhibitor of Metalloproteinase-1 / metabolism*
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
|
| IF |
4.679
|
| 引用数 |
7
|
|
WOS 分野
|
FOOD SCIENCE & TECHNOLOGY
TOXICOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
Hep G2 |
