Paper Details
- Masahiko Satoh (Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University / masahiko@dpc.agu.ac.jp)
1) Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University , 2) Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
Several metal(loid) toxicants can trigger cytotoxicity by causing apoptosis. Our previous study demonstrated that cadmium induces apoptosis by suppressing expression of the apoptosis inhibitor, BIRC3 [Baculoviral inhibition of apoptosis (IAP) protein repeat containing 3], in human proximal tubular cells (HK-2 cells). BIRC3 is a member of the BIRC family, which consists of eight family members in human, and seven in mouse. The observed suppression of BIRC3 gene expression was mostly specific to cadmium and to HK-2 cells. In this study, we examined whether methylmercury, inorganic mercury, or arsenic may affect the gene expression of other BIRC family members in several different cultured cells. Methylmercury decreased the level of BIRC2 mRNA and increased the level of BIRC5 mRNA in human IMR-32 neuroblastoma cells. Methylmercury increased the mRNA levels of BIRC2, BIRC5, and BIRC8 and decreased the mRNA levels of BIRC6 in HK-2 cells. Inorganic mercury increased the mRNA levels of BIRC2 and BIRC5 in HK-2 cells. Finally, arsenic increased the levels of Birc1 and Birc7 and decreased the levels of Birc2, Birc4, Birc5, and Birc6 mRNA in mouse normal hepatic AML-12 cells. Taken together, these results indicate that each metal(loid) toxicant may regulate the gene expression of BIRC family members in different manners. Therefore, each BIRC family member may play distinct roles when various tissues are exposed to toxic heavy metals or metalloid toxicants.