Induced secretion of insulin-like growth factor binding protein-1 (IGFBP-1) in human hepatoma cell HepG2 by rubratoxin B

被引：0
作者：
Hitoshi Nagashima
Kumiko Maeda-Nakamura
Keiko Iwashita
Tetsuhisa Goto
机构：
[1] National Food Research Institute,National Agriculture and Food Research Organization
[2] Shinshu University,Faculty of Agriculture
来源：
Archives of Toxicology | 2007年 / 81卷
关键词：
Rubratoxin B; Insulin-like growth factor binding protein-1 (IGFBP-1); Stress-activated MAP kinase (SAPK);
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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 μg/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.
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页码：347 / 351
页数：4
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  • [1] Bennett BL(2001)SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase Proc Natl Acad Sci USA 98 13681-13686
  • [2] Sasaki DT(1957)A disease of swine and cattle caused by eating moldy corn. II. Experimental production with pure cultures of molds Am J Vet Res 18 817-824
  • [3] Murray BW(2001)Mammalian MAP kinase signalling cascades Nature 410 37-40
  • [4] O’Leary EC(1990)Insulin regulation of insulin-like growth factor-binding protein production in cultured HepG2 cells J Clin Endocrinol Metab 70 1062-1067
  • [5] Sakata ST(2004)Matrix metalloproteinase-3 and -9 proteolyze insulin-like growth factor-binding protein-1 Biol Reprod 71 438-443
  • [6] Xu W(1995)SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1 FEBS Lett 364 229-233
  • [7] Leisten JC(2000)Signal transduction by the JNK group of MAP kinases Cell 103 239-252
  • [8] Motiwala A(2000)Stimulation of insulin-like growth factor binding protein-1 synthesis by interleukin-1β: requirement of the mitogen-activated protein kinase pathway Endocrinology 141 3156-3164
  • [9] Pierce S(1997)Tissue inhibitors of metalloproteinases: structure, regulation and biological functions Eur J Cell Biol 74 111-122
  • [10] Satoh Y(2005)Effects of genetics, sex, and age on the toxicity of rubratoxin B in mice Mycotoxins 55 35-42
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