亚砷酸盐诱导的信号转导需要蛋白激酶C（PKC）的激活。

Activation of PKC is required for arsenite-induced signal transduction.

作者信息

Chen N Y, Ma W Y, Huang C, Ding M, Dong Z

机构信息

The Hormel Institute, University of Minnesota, Austin 55912, USA.

出版信息

J Environ Pathol Toxicol Oncol. 2000;19(3):297-305.

PMID:10983896

Abstract

Trivalent arsenic (arsenite) is a human carcinogen. However, the molecular mechanism of arsenite-induced carcinogenesis is still not well understood. In this study, we found that arsenite induced translocation of PKCepsilon, PKCdelta, and PKCalpha from cytosol to membranes. Rottlerin, a selective inhibitor for PKCdelta, and safingol, a specific inhibitor for PKCalpha, both markedly inhibited arsenite-induced AP-1 activity. These inhibitory effects by rottlerin and safingol appeared to be dose dependent. Arsenite-induced phosphorylation of Erks was inhibited by rottlerin, while safingol inhibited arsenite-induced phosphorylation of JNKs and p38 kinases. Dominant negative mutant transfectant of PKCepsilon markedly blocked arsenite-induced AP-1 activity and the phosphorylation of Erks, JNKs, and p38 kinases. These data demonstrate that PKCdelta, PKCepsilon, and PKCalpha mediate arsenite-induced AP-1 activation in JB6 cells through different MAP kinase (Erks, JNKs, and p38 kinases) pathways.

摘要

三价砷（亚砷酸盐）是一种人类致癌物。然而，亚砷酸盐诱导致癌作用的分子机制仍未完全阐明。在本研究中，我们发现亚砷酸盐可诱导蛋白激酶Cε（PKCε）、蛋白激酶Cδ（PKCδ）和蛋白激酶Cα（PKCα）从胞质溶胶转位至细胞膜。rottlerin是PKCδ的选择性抑制剂，safingol是PKCα的特异性抑制剂，二者均显著抑制亚砷酸盐诱导的活化蛋白-1（AP-1）活性。rottlerin和safingol的这些抑制作用呈剂量依赖性。rottlerin抑制亚砷酸盐诱导的细胞外信号调节激酶（Erks）磷酸化，而safingol抑制亚砷酸盐诱导的应激活化蛋白激酶（JNKs）和p38激酶磷酸化。PKCε的显性负性突变转染体显著阻断亚砷酸盐诱导的AP-1活性以及Erks、JNKs和p38激酶的磷酸化。这些数据表明，PKCδ、PKCε和PKCα通过不同的丝裂原活化蛋白激酶（Erks、JNKs和p38激酶）途径介导亚砷酸盐诱导的JB6细胞中AP-1的活化。