PP2A B56α亚基介导镉诱导的细胞毒性

doi:10.3969/j.issn.1004-616x.2015.01.003

Abstract

Abstract:

OBJECTIVE: To identify involvement of protein phosphatase 2A B56α in 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 different concentrations of CdCl2 or 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 were significantly 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 were reduced by 35%-38% (P<0.05) and 13%-35%(P<0.05)，respectively，while cytotoxicity 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) in a time-dependent manner upon CdCl2 treatment. CONCLUSION：PP2A B56α regulated MT expression via dephosphorylating JNK，and affecting the cytotoxicity induced by CdCl2. Our study demonstrated that PP2A B56α participated in regulating the targets and pathways in response to metallic stress.

Key words: CdCl2, cytotoxicity, protein phosphatase 2A, p-JNK, metallothionein

LI Miao，MA Lu，BAI Qing，CHEN Wen，CHEN Liping. Role of PP2A B56α subunit in cadmium-induced cytotoxicity[J]. Carcinogenesis, Teratogenesis & Mutagenesis, doi: 10.3969/j.issn.1004-616x.2015.01.003.

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Role of PP2A B56α subunit in cadmium-induced cytotoxicity

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