The MARCKS protein amount is differently regulated by calpain during toxiceffects of methylmercury between SH-SY5Y and EA.hy926 cells

[摘要] Methylmercury (MeHg) is an environmental pollutant that shows severe toxicity to humansand animals. However, the molecular mechanisms mediating MeHg toxicity are not completelyunderstood. We have previously reported that the MARCKS protein is involved in the MeHgtoxicity to SH-SY5Y neuroblastoma and EA.hy926 vascular endothelial cell lines. Inaddition, calpain, a Ca2+-dependent protease, is suggested to be associatedwith the MeHg toxicity. Because MARCKS is known as a substrate of calpain, we studied therelation between calpain activation and cleavage of MARCKS and its role in MeHg toxicity.In SH-SY5Y cells, MeHg decreased cell viability along with increased calcium mobilization,calpain activation and a decrease in MARCKS amounts. However, pretreatment with calpaininhibitors attenuated the decrease in cell viability and MARCKS amount induced only by 1µM but not by 3 µM MeHg. In cells with a MARCKSknockdown, calpain inhibitors failed to attenuate the decrease in cell viability caused byMeHg. In EA.hy926 cells, although MeHg caused calcium mobilization and a decrease inMARCKS levels, calpain activation was not observed. These results indicate that theparticipation of calpain in the regulation of MARCKS amounts is dependent on the cell typeand concentration of MeHg. In SH-SY5Y cells, calpain-mediated proteolysis of MARCKS isinvolved in cytotoxicity induced by a low concentration of MeHg.

[学科分类] 兽医学

[关键词] calpain;MARCKS;methylmercury