Induction of endoplasmic reticulum stress and the modulation of thioredoxin-1 in formaldehyde-induced neurotoxicity

• DOI: 10.1016/j.neuro.2012.02.004
• Publication Date: 2012-02-10T14:45:51Z
• Authors: Fu-Cheng Luo; Jia Zhou; Tao Lv; Lei Qi; Sheng-Dong Wang; Hajime Nakamura; Junji Yodoi; Jie Bai
• Keywords: Neurons; 0301 basic medicine; Dose-Response Relationship, Drug; Ginsenosides; Cell Survival; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; PC12 Cells; Rats; 3. Good health; 03 medical and health sciences; Neuroprotective Agents; Thioredoxins; Gene Expression Regulation; Cytoprotection; Formaldehyde; Animals; Environmental Pollutants; Neurotoxicity Syndromes; RNA Interference; Endoplasmic Reticulum Chaperone BiP; Caspase 12; Heat-Shock Proteins

Formaldehyde (FA), a common environmental pollutant, has toxic effects on central nervous system. The detailed mechanisms on FA-induced neurotoxicity have not been fully elucidated. In this study, we found that glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) expression, biomarkers of endoplasmic reticulum (ER) stress, were increased and pro-caspase-12 was decreased after PC12 cells exposure to FA. These results suggest that FA actually induces ER stress. Thioredoxin-1 (Trx-1) has various biological activities, including the control of redox balance, the modulation of ER stress and inhibition of apoptosis. In the present study, Trx-1 expression was increased at early stage, but decreased at late stage after FA treatment. Knockdown of Trx-1 expression increased the susceptibility of PC12 cells to FA-induced neurotoxicity. We also found that ginsenoside Rg1 had the potential to induce Trx-1 expression and attenuated neurotoxicity induced by FA. ER stress caused by FA was suppressed by ginsenoside Rg1. These data indicate that Trx-1 is a therapeutic candidate for protecting against FA-induced neurotoxicity.