Sato Hidesuke, Nomata Koichiro, Noguchi Mitsuru, Takahashi Hajime, Watanabe Jun-Ichi, Kanetake Hiroshi
Department of Urology, Nagasaki University School of Medicine, Sakamoto 1-7-1, Nagasaki, Japan 852-8501.
Anticancer Res. 2003 May-Jun;23(3B):2565-8.
Dimethylnitrosamine(DMN) is an alkylating agent and a known renal carcinogen. A short exposure of renal epithelial cells to cytotoxic concentrations of DMN influences the expression of gap junction proteins. In this study, we examined gap junctional intercellular communication and connexin 43 expression in renal epithelial cells treated with 1% DMN and also examined the effects of dibutyryl-cAMP on preventing gap junctional disturbances. Connexin 43 becomes hypophosphorylated after treatment with 1% DMN for 15 minutes, but this hypophosphorylation is inhibited by pretreatment with dibutyryl-cAMP. These results suggest that changes in gap junction protein expression are early events associated with 1% DMN treatment of renal epithelial cells, and such changes are prevented by dibutyryl-cAMP pretreatment.
二甲基亚硝胺（DMN）是一种烷化剂，也是一种已知的肾致癌物。将肾上皮细胞短暂暴露于细胞毒性浓度的DMN会影响间隙连接蛋白的表达。在本研究中，我们检测了用1% DMN处理的肾上皮细胞中的间隙连接细胞间通讯和连接蛋白43的表达，并研究了二丁酰环磷腺苷（dibutyryl-cAMP）对预防间隙连接紊乱的作用。用1% DMN处理15分钟后，连接蛋白43发生低磷酸化，但这种低磷酸化可被二丁酰环磷腺苷预处理所抑制。这些结果表明，间隙连接蛋白表达的变化是1% DMN处理肾上皮细胞相关的早期事件，而二丁酰环磷腺苷预处理可预防此类变化。
