- Yaichiro Kotake (Graduate School of Biomedical and Health Sciences, Hiroshima University / firstname.lastname@example.org)
1) Graduate School of Biomedical and Health Sciences, Hiroshima University , 2) Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University , 3) Research Fellow of the Japan Society for the Promotion of Science
Organotin compounds such as triphenyltin (TPT), which are common environmental pollutants, had been widely used as antifouling agents for ship bottoms. Although toxic effects of organotins through nuclear receptors such as retinoid X receptor (RXR) and peroxisome proliferator-activated receptor (PPAR) γ have been well demonstrated, other mechanisms underlying organotin-induced toxicity have hardly been reported. In the present study, we focused on the transcription factor GA-binding protein (GABP), which regulates the expression of various housekeeping genes, as a novel target of TPT toxicity. We investigated the change of GABPα subunit protein expression induced by TPT. Although 100-500 nM concentration of TPT was not found to affect the total protein expression of GABPα, TPT significantly decreased nuclear translocation of GABPα in human embryonic kidney (HEK) 293T cells. In addition, TPT increased intracellular reactive oxygen species (ROS) levels. Both inhibition of GABPα nuclear translocation and the increase in ROS levels were observed in menadione (an ROS inducer)-treated HEK293T cells. Our results indicate that TPT causes inhibition of GABPα nuclear translocation, which may be triggered by ROS production. This might have serious implications in cellular physiology, thereby affecting cell survival.