Cellular biological study on mechanisms of acrylamide toxicity and its prevention

丙烯酰胺毒性机制及防治的细胞生物学研究

• 批准号: 12670335
• 负责人: IGISU Hideki
• 金额: $ 2.05万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670335/
• 关键词: acrylamide; encephalopathy; magnetic resonance; immediate early genes; c-Fos; c-Jun; mitogen actibated protein kinase; c-Fos; c-Jun; 神経毒; 磁気共鳴

Utilizing ultra-high field magnetic resonance (MR), we found that acrylamide (50 mg/kg/day, 8 days, i.p.) causes morphological alterations in the rat brain (enlargement of ventricles and cisterns, thinning of cortex). Before this, we showed that MR is a very powerful tool to investigate changes in the rat brain caused by hexachlorophene. Since it was reported that acrylamide induced c-Fos, one of the immediate early genes, in the brain, we used pentylenetetrazol (PTZ), an established potent inducer of c-Fos, and found that PTZ causes increase of mRNA of c-Fos in the mouse brain and that it can be suppressed by L-carnitine. We also found that various chemicals activate mitogen activated protein kinase (MAPK) and that calcium is important in some cases. Based on these, we examined effects of acrylamide on human neuroblastoma SH/SY5Y cells. Acrylamide caused cell toxicity after incubation for 48-72 hours. Whereas it did not cause significant increase of c-Fos mRNA, exposure to acrylamide increased c-Jun mRNA. Nevertheless, no activation of MAPKs (ERK, JNK, p38) was found.

利用超高场磁共振(MR)，我们发现丙烯酰胺(50 mg/kg/d，8天，i.p.)导致大鼠大脑的形态变化(脑室和脑池增大，皮质变薄)。在此之前，我们展示了MR是研究六氯酚引起的大鼠大脑变化的一个非常强大的工具。鉴于已有报道丙烯酰胺可诱导脑内即刻早期基因c-Fos的表达，我们使用已被证实的c-Fos诱导剂戊四唑，发现PTZ可引起小鼠脑内c-Fos基因表达增加，并可被L肉碱所抑制。我们还发现，不同的化学物质激活了丝裂原活化蛋白激酶(MAPK)，在某些情况下，钙是重要的。在此基础上，我们检测了丙烯酰胺对人神经母细胞瘤SH/SY5Y细胞的影响。丙烯酰胺在孵育48-72小时后即可引起细胞毒性。丙烯酰胺对c-Fos基因表达无明显影响，但可使c-Jun基因表达增加。但未发现MAPKs(ERK、JNK、p38)被激活。

项目成果

荒記 俊一編 伊規須 英輝, 松岡 雅人: "中毒学 -基礎・臨床・社会医学-"朝倉書店. (2002)

荒木俊一、生须秀树、松冈正人编：《成瘾学-基础/临床/社会医学-》朝仓书店（2002）。

Kinoshita,Y.,Matsumura,H.,Igisu,H.,Yokota,A.: "Hexachlorophene-induced brain edema in rat observed by proton magnetic resonance"Brain Research. 873. 127-130 (2000)

Kinoshita，Y.，Matsumura，H.，Igisu，H.，Yokota，A.：“通过质子磁共振观察到的六氯酚诱导的大鼠脑水肿”脑研究。

Matsuoka M., Igisu H.: "Cadmium induces phosphorylation of p53 at serine 15 in MCF-7 cells"Biochemical and Biophysical Research Communications. 282・5. 1120-1125 (2001)

Matsuoka M.，Igisu H.：“镉诱导 MCF-7 细胞中 p53 丝氨酸 15 的磷酸化”，生物化学和生物物理研究通讯 282・5（2001）。

Matsuoka M., Igisu H.: "Cadmium induces phosphorylation of p53 at serine 15 in MCF-7 cells"Biochemical and Biophysical Research Communications. 282(5). 1120-1125 (2001)

Matsuoka M.，Igisu H.：“镉诱导 MCF-7 细胞中 p53 丝氨酸 15 的磷酸化”生物化学和生物物理研究通讯。

Kinoshita Y., Matsumura H., Igisu H., Yokota A.: "Hexachlorophene-induced brain edema in rat observed by proton magnetic resonance"Brain Research. 873(1). 127-130 (2000)

Kinoshita Y.、Matsumura H.、Igisu H.、Yokota A.：“通过质子磁共振观察到的六氯酚诱发的大鼠脑水肿”脑研究。