Mechanism of cellular damages caused by cholorophenol compounds and their prevention

氯酚类化合物损伤细胞的机制及其预防

• 批准号: 10670330
• 负责人: IGISU Hideki
• 金额: $ 1.66万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670330/
• 关键词: pentachlorophenol; hexachlorophene; cytotoxicity; c-Fos; c-Jun; mitogen-activated protein kinase; L-carnitine; N-acetylcysteine

Pentachloropheno1 (PCP) increased oxygen consumption and decreased repiratory control ratio in mitochondria from rat liver (J UOEH 20:315, 1998). These effects of PCP were suppressed by L-carnitine but those of pentylenetetrazol (PTZ) were not. Other findings of ours include ; N-acetylcysteine suppressed cytotoxicity of cadmium in LLC-PK1 cells (J Pharmacol Exp Therap 287:344, 1998) ; cadmium activated c-Jun N-terminal kinase (JNX) in the same cells (Biochem Biphys Res Commun 251:527, 1998) ; carnitine suppressed PTZ-induced c-fos expression in the mouse brain (J Occup Health, in press) ; toxicity of cadmium was greater in fibroblasts lacking c-fos (Biochem Pharmacol, in press). Nevertheless, cells lacking c-fos showed no definite difference from the controls in response to PCP and hexachlorophene (HCP). Neither PCP nor HCP caused clear activation of JNK, ERK and p-38, suggesting that signal transduction system to c-Fos and c-Jun may not be involved in inducing cellar toxicity of above chlorophenol compounds. However, it is likely that toxicity of PCP on mitochondria may be lessened by L-carnitine.

五氯苯酚（PCP）增加了大鼠肝脏线粒体的耗氧量，降低了呼吸控制率（J UOEH 20：315，1998年）。PCP的这些作用被L-肉毒碱抑制，而戊四氮（PTZ）的这些作用则不被抑制。我们的其他发现包括; N-乙酰半胱氨酸抑制LLC-PK 1细胞中镉的细胞毒性（J Pharmacol Exp Therap 287：344，1998）;在相同细胞中镉激活的c-Jun N-末端激酶（JNX）（Biochem Biphys Res Commun 251：527，1998）;肉毒碱抑制小鼠脑中PTZ诱导的c-fos表达（J Occup Health，出版中）;镉的毒性在缺乏c-fos的成纤维细胞中更大（Biochem Pharmacol，出版中）。然而，缺乏c-fos的细胞对PCP和六氯酚（HCP）的反应与对照组没有明显差异。PCP和HCP均未引起JNK、ERK和p-38的明显激活，提示c-Fos和c-Jun的信号转导系统可能不参与上述氯酚类化合物的细胞毒性。然而，L-肉碱可能会减轻五氯苯酚对线粒体的毒性。

项目成果

Iryo, Y.: "Suppression of pentylenetetrazol-induced seizures and c-fos expression in mouse brain by L-carnitine"Journal of Occuptaional Health. (in press).

Iryo, Y.：“左旋肉碱抑制戊四唑诱导的癫痫发作和小鼠大脑中 c-fos 的表达”职业健康杂志。

Matsuoka, M.: "Activation of c-Jun NH_2-terminal kinase (JUN/SAPK) in LLC-PK_1 cells by cadmium"Biochemical and Biophysical Research Communications. 251.2. 527-532 (1998)

Matsuoka, M.：“镉在 LLC-PK_1 细胞中激活 c-Jun NH_2 末端激酶 (JUN/SAPK)”生物化学和生物物理研究通讯。

Matsuoka,M.,et al.: "Increased cytotoxicity of cadmium in fibroblasts lacking c-fos"Biochemical Pharmacology. (in press).

Matsuoka,M.,et al.：“缺乏 c-fos 的成纤维细胞中镉的细胞毒性增加”生化药理学。

Matsuoka, M.: "Mercury chloride activates c-Jun N-terminal kinase and induces c-jun expression in LLC-PK_1 cells"Toxicological Sciences. 53.2. 361-368 (2000)

Matsuoka, M.：“氯化汞激活 c-Jun N 末端激酶并诱导 LLC-PK_1 细胞中的 c-jun 表达”毒理学科学。

Matsuoka, M., et al.: "Increased cytotoxicity of cadmium in fibroblats lacking c-fos"Biochemical Pharmacology. (in press).

Matsuoka, M., et al.：“缺乏 c-fos 的成纤维细胞中镉的细胞毒性增加”生化药理学。