Protection of Thioredoxin 1 against overexpression of metabotropic glutamate receptor 1a-induced toxicity

Objective To understand the mechanism of underlying agonist-independent cell death induced by metabotropic glutamate receptor la (mGluR1a) overexpression and the role of Thioredoxin (Trx1) in this mechanism of cell death. Methods Cell viability, intracellular reactive oxygen species (ROS), signaling pathways such as AKT, PARP, Bcl-2 and redox state of Trx1 were detected by MTT assay, DCF assay, Western blot and Redox western blot, respectively. Results With a decrease in cell viability, we found that ROS production as well as the splicing of PARP were augmented while the phosphorylation of AKT and the expression of an anti-apoptotic molecule, Bcl-2 were compromised in mGluR1a over-expressed HEK293 cells. We further detected the role of Trx1 in this process and found that overexpression of Trx1 could efficiently protect HEK293 cells from mGluR1a-induced cell death via its antioxidant function. In addition, the interaction of mGluR1a and Trx1 was not detected in the experiment. Conclusion mGluR1a induced production of ROS and cell death in HEK293 cells while Trx1 modulated cell death through scavenging intracellular ROS and regulating relevant signaling pathways.