癌变·畸变·突变Issue(1)：11-15,20,6.DOI:10.3969/j.issn.1004-616x.2015.01.003
PP2A B56α亚基介导镉诱导的细胞毒性
αRole of PP2A B56 subunit in cadmium-induced cytotoxicity
摘要
Abstract
OBJECTIVE:To identify involvement ofprotein phosphatase 2A B56αin the regulation of cytotoxicity induced by cadmium chloride (CdCl2) and address the underlying molecular mechanism.METHODS:Stable cell lines were generated by infecting HEK cells with lentiviral shRNA targeting B56α subunit. Modified MTT was performed to detect the cytotoxicity induced by CdCl2. Immunoblotting analysis was applied to examine the expressions of B56α,p-JNK and MT in cells treated with differentconcentrations ofCdCl2or co-treated with SP600125.RESULTS:Immunoblotting results verified that stable cell lines HEK-SHB56α-1 and HEK-SHB56α-2 were successfully established. We found that suppression of PP2A B56α reduced the cytotoxicity induced by CdCl2. In addition,the phosphorylation status of c-Jun N-terminal kinases (JNK)and the expression level of MT weresignificantly increased in response to CdCl2. Suppression of B56α led to a 2.78 or 1.26-fold(P<0.05) increase of p-JNK in cells treated with CdCl2 for 12 h,and a 1.36 or 1.19-fold (P<0.05) increase of MT. Upon SP600125 treatment,the expression level of p-JNK and MT werereduced by 35%-38% (P<0.05) and 13%-35%(P<0.05),respectively,whilecytotoxicity induced by CdCl2 was enhanced(P<0.05). More-over,the expression of B56α was lowered(P<0.05),but p-JNK and MT were increased(P<0.05) inatime-dependent manner upon CdCl2 treatment. CONCLUSION:PP2A B56α regulated MT expression via dephosphorylating JNK,and affecting the cytotoxicity induced by CdCl2. Our study demonstratedthat PP2A B56α participated in regulating the targets and pathways in response to metallic stress.关键词
氯化镉/细胞毒性/蛋白磷酸酶2A/p-JNK/金属硫蛋白Key words
CdCl2/cytotoxicity/protein phosphatase 2A/p-JNK/metallothionein分类
医药卫生引用本文复制引用
李妙,马璐,柏青,陈雯,陈丽萍..PP2A B56α亚基介导镉诱导的细胞毒性[J].癌变·畸变·突变,2015,(1):11-15,20,6.基金项目
国家自然科学基金青年基金项目(31401213) （31401213）
