›› 2012, Vol. 24 ›› Issue (3): 189-194.doi: 10.3969/j.issn.1004-616x.2012.03.006

• 论著 • Previous Articles     Next Articles

Overexpression of PP2A-B56γ repressed the effect of cadmium on DNA damage in human normal L02 liver cells

LIN Li-na，LIN Yu-chun，CHEN Hui-feng，LUO Jie，LI Xiao-jie，HU Yao-ming，LI Wen，ZHANG Shu-jiang，CHEN Wen，LIN Zhong-ning   

  1. School of Public Health, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, Guangdong, China
  • Received:2011-04-28 Revised:2012-02-10 Online:2012-05-30 Published:2012-05-30
  • Contact: LIN Zhong-ning

PDF (PC)

851

Abstract: OBJECTIVE: To investigate the effects of protein phosphatase 2A (PP2A)-B56γ subunit (encoded by PPP2R5C gene) overexpression on cadmiun-induced gene transcription and DNA damage in human normal liver L02 cells. METHODS：Cell models were established via stable transfection with overexpression PPP2R5C (L02-2R5Cc) and null vector pBabe-puro (L02-pBabe). QRT-PCR was used to detect the effects of cadmium and TNFα on PPP2R5C and MT1B mRNA expression. SCGE assay was adopted to evaluate their genotoxicity. The 3 × 2 factorial analysis experiment was aimed to explore the type of their combined effects. RESULTS：The levels of total and exogenous (PPP2R5C-FLAG) PPP2R5C mRNA were markedly elevated in L02-2R5Cc cells compared with L02-pBabe cells，and reduced by treatments with cadmium and TNFα (P<0.05). The level of MT1B mRNA was induced by cadmium but reduced by TNFα and PPP2R5C overexpression (P<0.05). Factorial ANOVA analysis revealed that，in terms of the mRNA levels of PPP2R5C and PPP2R5C-FLAG，synergistic enhanced effects were showed between PPP2R5C overexpression and cadmium treatment，also PPP2R5C overexpression and TNFα treatment (P<0.05). While on MT1B mRNA expression，there was antagonistic effect between PPP2R5C overexpression and cadmium as well as between cadmium and TNFα，but synergistic inhibitory effect between PPP2R5C overexpression and TNFα (P<0.05). DNA damage was significantly induced by cadmium (P<0.05)，but not detected by TNFα nor PPP2R5C overexpression (P > 0.05). Further factorial analysis suggested synergistic effects were found between cadmium and TNFα，but antagonistic effect between cadmium and PPP2R5C overexpression (P<0.05). No interaction was noted between PPP2R5C overexpression and TNFα (P> 0.05). CONCLUSION：Cadmium suppressed PPP2R5C gene transcription and significantly induced DNA damage. PP2A-B56γ overexpression repressed the genotoxicity induced by cadmium，which was enhanced in the presence of inflammatory factor.

Key words: protein phosphatase 2A (PP2A), regulatory B56γ subunit, cadmium, hepatotoxicity, transcription regulation

CLC Number: